Patients with obstructive sleep apnea (OSA) frequently present with symptoms of depression and an... more Patients with obstructive sleep apnea (OSA) frequently present with symptoms of depression and anxiety. The objective of this study is to determine if treatment with positive airway pressure (PAP) improves symptoms of depression and anxiety. A systematic review was conducted to identify clinical trials of PAP that contained a validated measure of depression severity. Meta-analysis was conducted for depression, anxiety, excessive daytime sleepiness (EDS), quality of life (QoL) and respiratory variables. The systematic review included 33 reports. Pre-post-test analysis of PAP showed a moderate effect size (Hedge's g, 95% CI) for depression 0.524 [0.401-0.647], but a low effect size compared to oral placebo (0.355 [0.187-0.524]) and no effect when compared to dental appliances (0.107 [-0.72-0.287]) and sham PAP (-0.049 [-0.292-0.194]). Anxiety, EDS, and QoL showed similar improvement in pre-post-test analysis, but a lack of superiority to dental appliances and sham PAP. PAP was sup...
Psoriasis is an immune-mediated chronic inflammatory disorder which manifests as dermatologic les... more Psoriasis is an immune-mediated chronic inflammatory disorder which manifests as dermatologic lesions, and psoriatic arthritis (PsA) in about 30% of cases. Psoriasis is associated with multiple comorbidities including metabolic syndrome, hypertension, diabetes, cardiovascular events, obesity and psychiatric disorders, which can all affect the course of sleep disorders. A systematic review of the literature on the relationship between psoriasis, PsA, and formal sleep disorders identified 33 studies. There is an increased prevalence of obstructive sleep apnea (OSA) with 36%e81.8% prevalence in psoriasis versus 2%e4% in the general population. There was also an increase in the prevalence of restless legs syndrome of 15.1%e18% in psoriasis versus 5%e10% in European and North American samples. The wide variety of insomnia criteria used in studies resulted in an insomnia prevalence of 5.9%e44.8% in psoriasis, which is insufficient to show an elevated prevalence when the general population has a 10% prevalence of chronic insomnia and 30e35% prevalence of transient insomnia. There is evidence that symptoms of insomnia in psoriasis are directly mediated by pruritus and pain. Treatments that decrease the cutaneous symptoms in psoriasis were successful in mitigating insomnia, but did not show improvements in OSA where the relationship with psoriasis is multifactorial.
The Journal of dermatological treatment, Jan 18, 2015
The route of antifungal drug entry into the nail plate and the underlying nail bed plays an impor... more The route of antifungal drug entry into the nail plate and the underlying nail bed plays an important role in determining the efficacy of therapy. Oral antifungal agents reach the nail bed and nail plate by being ingested and achieving antifungal levels in the blood stream that are well in excess of the minimum inhibitory concentration. The reticular circulation at the distal end of the digit enables the drug to reach the nail bed, the proximal matrix and the lateral nail folds. The drug then diffuses into the proximal, ventral and lateral nail plate. The primary route of drug delivery for topical lacquers is transungual, with drug applied to the dorsal aspect of the nail plate and penetrating to the underlying nail bed. The new topical agents approved in the US for the treatment of onychomycosis are solutions with lower viscosity and increased nail penetration characteristics; therefore, these agents penetrate through the transungual route, but also through the space between the na...
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, Jan 15, 2015
Obstructive sleep apnea (OSA) has been associated with psychiatric pathology. Psychiatric comorbi... more Obstructive sleep apnea (OSA) has been associated with psychiatric pathology. Psychiatric comorbidity in OSA may affect patient quality of life and adherence to CPAP. A focused evaluation of OSA in highly selected groups of primarily psychiatric patients may provide further insights into the factors contributing to comorbidity of OSA and psychopathology. The goal of this study is to examine the prevalence and treatment of OSA in psychiatric populations. A systematic review following the PRISMA guidelines was conducted to determine the prevalence of OSA in schizophrenia and other psychotic disorders, mood disorders, and anxiety disorders, and to examine potential interventions. The PubMed, EMBASE, and PsycINFO databases were searched (last search April 26, 2014) using keywords based on the ICD-9-CM coding for OSA and the DSM-IV-TR diagnostic groups. The search retrieved 47 records concerning studies of OSA in the selected disorders. The prevalence studies indicate that there may be a...
Device-based therapies are promising alternatives for the treatment of onychomycosis because they... more Device-based therapies are promising alternatives for the treatment of onychomycosis because they can mitigate some of the negative factors associated with treatment failure. There are four categories of device-based treatments: laser devices, photodynamic therapy, iontophoresis, and ultrasound. These therapeutic modalities are noninvasive procedures that are carried out by medical professionals, reduce the need for long-term patient adherence, and avoid adverse reactions associated with conventional systemic antifungal therapies.
Efinaconazole is an emerging antifungal therapy for the topical treatment of onychomycosis. Efina... more Efinaconazole is an emerging antifungal therapy for the topical treatment of onychomycosis. Efinaconazole is an inhibitor of sterol 14α-demethylase and is more effective in vitro than terbinafine, itraconazole, ciclopirox and amorolfine against dermatophytes, yeasts and non-dermatophyte molds. Phase II studies indicate that efinaconazole 10% nail solution is more effective than either the 5% strength or 10% solution with semi-occlusion. In duplicate Phase III clinical trials, complete cure rates of 17.8% and 15.2% were demonstrated. The mean mycological cure rate for efinaconazole is similar to the oral antifungal itraconazole and exceeds the efficacy of topical ciclopirox. Efinaconazole showed minimal localized adverse events, which ceased upon stopping treatment. Overall, efinaconazole 10% nail solution is an effective topical monotherapy for distal and lateral subungual onychomycosis (<65% nail involvement, excluding the matrix) that shows further potential use as an adjunct t...
Topical therapies for onychomycosis are associated with less adverse events than systemic therapi... more Topical therapies for onychomycosis are associated with less adverse events than systemic therapies, but poor nail penetration limits their efficacy. Consequently, an efinaconazole 10% nail solution was developed. To review the evidence supporting the usefulness of efinaconazole monotherapy in onychomycosis management. PubMed and clinicaltrials.gov databases and abstracts from the 2013 annual meeting of the American Academy of Dermatology were searched in April 2013 using the terms "efinaconazole," "IDP-108," and "KP-103." In vitro, efinaconazole possesses a broad antifungal activity similar or superior to that of other antifungals. Its low affinity for keratin results in good nail penetration. Efinaconazole 10% nail solution administered daily for 36 or 48 weeks to treat mild to moderate toenail onychomycosis caused by dermatophytes results in complete and mycologic cure rates of 15 to 25% and 53 to 87%, respectively. No serious skin reaction is associ...
Efinaconazole 10% nail solution (Jublia(®)) is a new topical triazole antifungal designed for the... more Efinaconazole 10% nail solution (Jublia(®)) is a new topical triazole antifungal designed for the topical treatment of distal and lateral subungual onychomycosis. It inhibits ergosterol biosynthesis enzyme sterol 14α-demethylase. Efinaconazole has lower minimum inhibitory concentrations than terbinafine, ciclopirox, itraconazole and amorolfine in Trichophyton rubrum, Trichophyton mentagrophytes and Candida albicans. The solution based formula has low surface tension and keratin binding properties that increase penetrance through the nail plate. Safety studies have shown that this formulation is not associated with atopic dermatitis or contact sensitivity. Duplicate Phase III clinical trials in adults with mild to moderate distal and lateral subungual onychomycosis indicate that efinaconazole 10% solution is an effective therapy with a pooled complete cure rate of 17% and a pooled mycological cure rate of 54%. Efinaconazole 10% nail solution is a safe and effective new topical therap...
Onychomycosis is an infection of the nail plate that is an important priority area for the develo... more Onychomycosis is an infection of the nail plate that is an important priority area for the development of antifungal drugs. The high incidence of relapse and reinfection often makes onychomycosis a chronic condition. The current gold standard is oral therapy, but the development of effective topical agents remains a priority as they have fewer systemic interactions. This review summarizes development of antifungals from early phase development through Phase III clinical trials for onychomycosis. The oral molecules in development are azole molecules. Topical drugs in development include azoles, allylamines, benzoxaboroles and nanoemulsions. Photosensitizers for photodynamic therapy and new laser systems are also emerging therapeutic options. There is a diverse array of antifungal drugs in the early phases of development. The goals of onychomycosis therapy are a mycological cure and a normal appearing nail. The recent development of topical antifungals has been successful at improving...
Laser therapy is a rapidly expanding new treatment modality for onychomycosis. To review current ... more Laser therapy is a rapidly expanding new treatment modality for onychomycosis. To review current and prospective laser systems for the treatment of onychomycosis. We searched the PubMed database, the Food and Drug Administration 510(k) database, ClinicalTrials.gov, and Google Scholar for in vitro studies, peer-reviewed clinical trials, manufacturers&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; white papers, and registered clinical trials of laser systems indicated for the treatment of onychomycosis. All published clinical trials were assessed on a 20-point methodological quality scale. We identified three basic science articles, five peer-reviewed articles, three white papers, and four pending clinical trials, as well as numerous gray literature documents. The overall methodological score for the clinical trials was 9.1 ± 1.1, with peer-reviewed studies showing a higher score (9.8 ± 1.5) than white papers (7.5 ± 0.7). We also identified 11 commercial laser device systems of varying global availability. Laser therapy has been tested and approved as a cosmetic treatment only for onychomycosis. It cannot be recommended as a therapeutic intervention to eradicate fungal infection at this time as more rigorous randomized, controlled trials are required to determine if laser therapy is efficacious on par with oral and topical interventions.
The variability in susceptibility to onychomycosis for individuals exposed to the same environmen... more The variability in susceptibility to onychomycosis for individuals exposed to the same environmental risk factors raises the possibility that there may be individuals with a genetic predisposition to dermatophyte infection. To determine whether there are genetic mutations or genotypes which contribute to onychomycosis. The PubMed database was searched for examples of immune deficiencies resulting in dermatophyte infections. There are mutations in the innate immune receptors Dectin-1 and its adaptor protein CARD9 which result in familial mucocutaneous infections. There are also specific human leukocyte antigen genotypes that are more common in individuals and families with a high prevalence of onychomycosis. In addition, some patients have been reported with insufficient levels of CD4+CD25+ regulatory T cells. These deficits impair a full innate and adaptive immune response and may result in chronic or recurrent infections. There are documented mutations and genotypes that contribute to familial and individual susceptibility to onychomycosis.
Journal of the American Podiatric Medical Association, 2012
Laser systems are a new treatment area for onychomycosis. As of January 2012, the US Food and Dru... more Laser systems are a new treatment area for onychomycosis. As of January 2012, the US Food and Drug Administration (FDA) has approved four laser systems for the “temporary increase of clear nail in onychomycosis.” The FDA has approved these devices on the basis of “substantial equivalence” to predicate devices with similar technical specifications and applications. Laser therapy appears to be a promising alternative to traditional pharmacotherapy, but these systems have been tested in only limited clinical trials; therefore, it is not possible to compare their efficacy to the oral and topical drugs currently used in the treatment of onychomycosis. (J Am Podiatr Med Assoc 102 (5): 428-430, 2012)
Journal of the American Academy of Dermatology, 2012
Background: Nondermatophyte mold (NDM) onychomycosis is difficult to diagnose given that NDMs are... more Background: Nondermatophyte mold (NDM) onychomycosis is difficult to diagnose given that NDMs are common contaminants of the nails and of the mycology laboratory. Diagnostic criteria and definition of cure are inconsistent between studies, which may affect the quality of published data. Due to the relative paucity of data on nondermatophyte molds, little is known about the clinical presentations associated with different organisms, epidemiology, or best treatment strategies available.
Patients with obstructive sleep apnea (OSA) frequently present with symptoms of depression and an... more Patients with obstructive sleep apnea (OSA) frequently present with symptoms of depression and anxiety. The objective of this study is to determine if treatment with positive airway pressure (PAP) improves symptoms of depression and anxiety. A systematic review was conducted to identify clinical trials of PAP that contained a validated measure of depression severity. Meta-analysis was conducted for depression, anxiety, excessive daytime sleepiness (EDS), quality of life (QoL) and respiratory variables. The systematic review included 33 reports. Pre-post-test analysis of PAP showed a moderate effect size (Hedge's g, 95% CI) for depression 0.524 [0.401-0.647], but a low effect size compared to oral placebo (0.355 [0.187-0.524]) and no effect when compared to dental appliances (0.107 [-0.72-0.287]) and sham PAP (-0.049 [-0.292-0.194]). Anxiety, EDS, and QoL showed similar improvement in pre-post-test analysis, but a lack of superiority to dental appliances and sham PAP. PAP was sup...
Psoriasis is an immune-mediated chronic inflammatory disorder which manifests as dermatologic les... more Psoriasis is an immune-mediated chronic inflammatory disorder which manifests as dermatologic lesions, and psoriatic arthritis (PsA) in about 30% of cases. Psoriasis is associated with multiple comorbidities including metabolic syndrome, hypertension, diabetes, cardiovascular events, obesity and psychiatric disorders, which can all affect the course of sleep disorders. A systematic review of the literature on the relationship between psoriasis, PsA, and formal sleep disorders identified 33 studies. There is an increased prevalence of obstructive sleep apnea (OSA) with 36%e81.8% prevalence in psoriasis versus 2%e4% in the general population. There was also an increase in the prevalence of restless legs syndrome of 15.1%e18% in psoriasis versus 5%e10% in European and North American samples. The wide variety of insomnia criteria used in studies resulted in an insomnia prevalence of 5.9%e44.8% in psoriasis, which is insufficient to show an elevated prevalence when the general population has a 10% prevalence of chronic insomnia and 30e35% prevalence of transient insomnia. There is evidence that symptoms of insomnia in psoriasis are directly mediated by pruritus and pain. Treatments that decrease the cutaneous symptoms in psoriasis were successful in mitigating insomnia, but did not show improvements in OSA where the relationship with psoriasis is multifactorial.
The Journal of dermatological treatment, Jan 18, 2015
The route of antifungal drug entry into the nail plate and the underlying nail bed plays an impor... more The route of antifungal drug entry into the nail plate and the underlying nail bed plays an important role in determining the efficacy of therapy. Oral antifungal agents reach the nail bed and nail plate by being ingested and achieving antifungal levels in the blood stream that are well in excess of the minimum inhibitory concentration. The reticular circulation at the distal end of the digit enables the drug to reach the nail bed, the proximal matrix and the lateral nail folds. The drug then diffuses into the proximal, ventral and lateral nail plate. The primary route of drug delivery for topical lacquers is transungual, with drug applied to the dorsal aspect of the nail plate and penetrating to the underlying nail bed. The new topical agents approved in the US for the treatment of onychomycosis are solutions with lower viscosity and increased nail penetration characteristics; therefore, these agents penetrate through the transungual route, but also through the space between the na...
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, Jan 15, 2015
Obstructive sleep apnea (OSA) has been associated with psychiatric pathology. Psychiatric comorbi... more Obstructive sleep apnea (OSA) has been associated with psychiatric pathology. Psychiatric comorbidity in OSA may affect patient quality of life and adherence to CPAP. A focused evaluation of OSA in highly selected groups of primarily psychiatric patients may provide further insights into the factors contributing to comorbidity of OSA and psychopathology. The goal of this study is to examine the prevalence and treatment of OSA in psychiatric populations. A systematic review following the PRISMA guidelines was conducted to determine the prevalence of OSA in schizophrenia and other psychotic disorders, mood disorders, and anxiety disorders, and to examine potential interventions. The PubMed, EMBASE, and PsycINFO databases were searched (last search April 26, 2014) using keywords based on the ICD-9-CM coding for OSA and the DSM-IV-TR diagnostic groups. The search retrieved 47 records concerning studies of OSA in the selected disorders. The prevalence studies indicate that there may be a...
Device-based therapies are promising alternatives for the treatment of onychomycosis because they... more Device-based therapies are promising alternatives for the treatment of onychomycosis because they can mitigate some of the negative factors associated with treatment failure. There are four categories of device-based treatments: laser devices, photodynamic therapy, iontophoresis, and ultrasound. These therapeutic modalities are noninvasive procedures that are carried out by medical professionals, reduce the need for long-term patient adherence, and avoid adverse reactions associated with conventional systemic antifungal therapies.
Efinaconazole is an emerging antifungal therapy for the topical treatment of onychomycosis. Efina... more Efinaconazole is an emerging antifungal therapy for the topical treatment of onychomycosis. Efinaconazole is an inhibitor of sterol 14α-demethylase and is more effective in vitro than terbinafine, itraconazole, ciclopirox and amorolfine against dermatophytes, yeasts and non-dermatophyte molds. Phase II studies indicate that efinaconazole 10% nail solution is more effective than either the 5% strength or 10% solution with semi-occlusion. In duplicate Phase III clinical trials, complete cure rates of 17.8% and 15.2% were demonstrated. The mean mycological cure rate for efinaconazole is similar to the oral antifungal itraconazole and exceeds the efficacy of topical ciclopirox. Efinaconazole showed minimal localized adverse events, which ceased upon stopping treatment. Overall, efinaconazole 10% nail solution is an effective topical monotherapy for distal and lateral subungual onychomycosis (<65% nail involvement, excluding the matrix) that shows further potential use as an adjunct t...
Topical therapies for onychomycosis are associated with less adverse events than systemic therapi... more Topical therapies for onychomycosis are associated with less adverse events than systemic therapies, but poor nail penetration limits their efficacy. Consequently, an efinaconazole 10% nail solution was developed. To review the evidence supporting the usefulness of efinaconazole monotherapy in onychomycosis management. PubMed and clinicaltrials.gov databases and abstracts from the 2013 annual meeting of the American Academy of Dermatology were searched in April 2013 using the terms "efinaconazole," "IDP-108," and "KP-103." In vitro, efinaconazole possesses a broad antifungal activity similar or superior to that of other antifungals. Its low affinity for keratin results in good nail penetration. Efinaconazole 10% nail solution administered daily for 36 or 48 weeks to treat mild to moderate toenail onychomycosis caused by dermatophytes results in complete and mycologic cure rates of 15 to 25% and 53 to 87%, respectively. No serious skin reaction is associ...
Efinaconazole 10% nail solution (Jublia(®)) is a new topical triazole antifungal designed for the... more Efinaconazole 10% nail solution (Jublia(®)) is a new topical triazole antifungal designed for the topical treatment of distal and lateral subungual onychomycosis. It inhibits ergosterol biosynthesis enzyme sterol 14α-demethylase. Efinaconazole has lower minimum inhibitory concentrations than terbinafine, ciclopirox, itraconazole and amorolfine in Trichophyton rubrum, Trichophyton mentagrophytes and Candida albicans. The solution based formula has low surface tension and keratin binding properties that increase penetrance through the nail plate. Safety studies have shown that this formulation is not associated with atopic dermatitis or contact sensitivity. Duplicate Phase III clinical trials in adults with mild to moderate distal and lateral subungual onychomycosis indicate that efinaconazole 10% solution is an effective therapy with a pooled complete cure rate of 17% and a pooled mycological cure rate of 54%. Efinaconazole 10% nail solution is a safe and effective new topical therap...
Onychomycosis is an infection of the nail plate that is an important priority area for the develo... more Onychomycosis is an infection of the nail plate that is an important priority area for the development of antifungal drugs. The high incidence of relapse and reinfection often makes onychomycosis a chronic condition. The current gold standard is oral therapy, but the development of effective topical agents remains a priority as they have fewer systemic interactions. This review summarizes development of antifungals from early phase development through Phase III clinical trials for onychomycosis. The oral molecules in development are azole molecules. Topical drugs in development include azoles, allylamines, benzoxaboroles and nanoemulsions. Photosensitizers for photodynamic therapy and new laser systems are also emerging therapeutic options. There is a diverse array of antifungal drugs in the early phases of development. The goals of onychomycosis therapy are a mycological cure and a normal appearing nail. The recent development of topical antifungals has been successful at improving...
Laser therapy is a rapidly expanding new treatment modality for onychomycosis. To review current ... more Laser therapy is a rapidly expanding new treatment modality for onychomycosis. To review current and prospective laser systems for the treatment of onychomycosis. We searched the PubMed database, the Food and Drug Administration 510(k) database, ClinicalTrials.gov, and Google Scholar for in vitro studies, peer-reviewed clinical trials, manufacturers&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; white papers, and registered clinical trials of laser systems indicated for the treatment of onychomycosis. All published clinical trials were assessed on a 20-point methodological quality scale. We identified three basic science articles, five peer-reviewed articles, three white papers, and four pending clinical trials, as well as numerous gray literature documents. The overall methodological score for the clinical trials was 9.1 ± 1.1, with peer-reviewed studies showing a higher score (9.8 ± 1.5) than white papers (7.5 ± 0.7). We also identified 11 commercial laser device systems of varying global availability. Laser therapy has been tested and approved as a cosmetic treatment only for onychomycosis. It cannot be recommended as a therapeutic intervention to eradicate fungal infection at this time as more rigorous randomized, controlled trials are required to determine if laser therapy is efficacious on par with oral and topical interventions.
The variability in susceptibility to onychomycosis for individuals exposed to the same environmen... more The variability in susceptibility to onychomycosis for individuals exposed to the same environmental risk factors raises the possibility that there may be individuals with a genetic predisposition to dermatophyte infection. To determine whether there are genetic mutations or genotypes which contribute to onychomycosis. The PubMed database was searched for examples of immune deficiencies resulting in dermatophyte infections. There are mutations in the innate immune receptors Dectin-1 and its adaptor protein CARD9 which result in familial mucocutaneous infections. There are also specific human leukocyte antigen genotypes that are more common in individuals and families with a high prevalence of onychomycosis. In addition, some patients have been reported with insufficient levels of CD4+CD25+ regulatory T cells. These deficits impair a full innate and adaptive immune response and may result in chronic or recurrent infections. There are documented mutations and genotypes that contribute to familial and individual susceptibility to onychomycosis.
Journal of the American Podiatric Medical Association, 2012
Laser systems are a new treatment area for onychomycosis. As of January 2012, the US Food and Dru... more Laser systems are a new treatment area for onychomycosis. As of January 2012, the US Food and Drug Administration (FDA) has approved four laser systems for the “temporary increase of clear nail in onychomycosis.” The FDA has approved these devices on the basis of “substantial equivalence” to predicate devices with similar technical specifications and applications. Laser therapy appears to be a promising alternative to traditional pharmacotherapy, but these systems have been tested in only limited clinical trials; therefore, it is not possible to compare their efficacy to the oral and topical drugs currently used in the treatment of onychomycosis. (J Am Podiatr Med Assoc 102 (5): 428-430, 2012)
Journal of the American Academy of Dermatology, 2012
Background: Nondermatophyte mold (NDM) onychomycosis is difficult to diagnose given that NDMs are... more Background: Nondermatophyte mold (NDM) onychomycosis is difficult to diagnose given that NDMs are common contaminants of the nails and of the mycology laboratory. Diagnostic criteria and definition of cure are inconsistent between studies, which may affect the quality of published data. Due to the relative paucity of data on nondermatophyte molds, little is known about the clinical presentations associated with different organisms, epidemiology, or best treatment strategies available.
Uploads
Papers by Fiona Simpson