Methylprednisolone dosing for pediatric critical asthma: a single-center cohort study.

OBJECTIVE: We aimed to characterize intravenous (IV) methylprednisolone (MP) dosing regimens and clinical outcomes for children hospitalized for critical asthma (CA). METHODS: A single-center, retrospective review was performed of children admitted to the pediatric intensive care unit (PICU) for CA between September 2015 and October 2019. Patients 5-to 17-year-olds, initiated on continuous nebulized albuterol, and prescribed at least one dose of IV MP were included. The primary outcome was to characterize PICU MP dosing. Cohorts were then compared by MP dosing: conservative-dose methylprednisolone (CDMP, ≤ 0.5 mg/kg/dose every 6 h) and standard-dose methylprednisolone (SDMP, > 0.5 mg/kg/dose every 6 h). Clinical efficacy endpoints were the duration of continuous nebulized albuterol and PICU length of stay (LOS). Safety endpoints included corticosteroid-related adverse events. RESULTS: Of 168 children studied, 50 (29.8%) were prescribed CDMP and 118 (70.2%) SDMP. The overall mean MP dose was 31.3 ± 19.6 mg (weight-adjusted: 0.77 ± 0.32 mg/kg/dose). Compared to those prescribed SDMP, those prescribed CDMP had a shorter median duration of continuous nebulized albuterol (12.8 [IQR: 10.5-20] versus 17.3 [IQR: 11.3-29.7] hours, p = 0.019) and median PICU LOS (0.9 [IQR: 0.7-1.4] versus 1.2 [IQR: 0.9-1.8] days, p = 0.012). No corticosteroid-related adverse events were observed. In adjusted models, weight-adjusted IV MP dose was not associated with PICU LOS or duration of continuous nebulized albuterol. CONCLUSIONS: Intravenous MP dosing for pediatric CA varied widely in our study sample. Prospective, controlled trials are required to validate our observations including clinical efficacy and safety endpoints.

Increasing Alprostadil Requirements in a Neonate With Cardiac Anomalies and Co-administration of Rectal and Oral Acetaminophen.

A patent ductus arteriosus (PDA) results from the failure of the ductus arteriosus to close within 72 hours after birth. In most neonates, a PDA can lead to significant morbidities and often warrants pharmacologic intervention for closure. Common pharmacologic interventions include indomethacin, ibuprofen, and acetaminophen. In cases of ductal-dependent congenital heart defects (CHDs), such as hypoplastic left heart syndrome, it is imperative to keep the ductus arteriosus patent to maintain adequate pulmonary or systemic circulation until surgical intervention can be performed. The only proven pharmacologic agent used for this indication is prostaglandin E1 (PGE1) commonly in the form of intravenous alprostadil. This case report describes a neonate with multiple cardiac and genetic anomalies that required increased alprostadil infusion after exposure to rectal and oral acetaminophen. The patient initially presented with a large PDA on echocardiogram (ECHO); however, after an incidental finding of a small PDA on ECHO, the administration of as needed rectal acetaminophen was discontinued out of concern for its effects on patency. After a few days of increased prostaglandin therapy and 2 reassuring ECHO results, the patient was given oral acetaminophen on an as needed basis. Within 24 hours of restarting the acetaminophen, the repeated ECHO showed a reduction in PDA and flow. In patients with ductal-dependent cardiac lesions, it is important to maintain PDA patency and, therefore, introducing a medication with antiprostaglandin properties should be avoided.

Acuity Assessment in Obstetrical Triage.

OBJECTIVE: A five-category Obstetrical Triage Acuity Scale (OTAS) was developed with a comprehensive set of obstetrical determinants. The purposes of this study were: (1) to compare the inter-rater reliability (IRR) in tertiary and community hospital settings and measure the intra-rater reliability (ITR) of OTAS; (2) to establish the validity of OTAS; and (3) to present the first revision of OTAS from the National Obstetrical Triage Working Group. METHODS: To assess IRR, obstetrical triage nurses were randomly selected from London Health Sciences Centre (LHSC) (n = 8), Stratford General Hospital (n = 11), and Chatham General Hospital (n= 7) to assign acuity levels to clinical scenarios based on actual patient visits. At LHSC, a group of nurses were retested at nine months to measure ITR. To assess validity, OTAS acuity level was correlated with measures of resource utilization. RESULTS: OTAS has significant and comparable IRR in a tertiary care hospital and in two community hospitals. Repeat assessment in a cohort of nurses demonstrated significant ITR. Acuity level correlated significantly with performance of routine and second order laboratory investigations, point of care ultrasound, nursing work load, and health care provider attendance. A National Obstetrical Triage Working Group was formed and guided the first revision. Four acuity modifiers were added based on hemodynamics, respiratory distress, cervical dilatation, and fetal well-being. CONCLUSION: OTAS is the first obstetrical triage scale with established reliability and validity. OTAS enables standardized assessments of acuity within and across institutions. Further, it facilitates assessment of patient care and flow based on acuity.

Adaptive significance of right hemisphere activation in aphasic language comprehension.

Aphasic patients often exhibit increased right hemisphere activity during language tasks. This may represent takeover of function by regions homologous to the left-hemisphere language networks, maladaptive interference, or adaptation of alternate compensatory strategies. To distinguish between these accounts, we tested language comprehension in 25 aphasic patients using an online sentence-picture matching paradigm while measuring brain activation with MEG. Linguistic conditions included semantically irreversible ("The boy is eating the apple") and reversible ("The boy is pushing the girl") sentences at three levels of syntactic complexity. As expected, patients performed well above chance on irreversible sentences, and at chance on reversible sentences of high complexity. Comprehension of reversible non-complex sentences ranged from nearly perfect to chance, and was highly correlated with offline measures of language comprehension. Lesion analysis revealed that comprehension deficits for reversible sentences were predicted by damage to the left temporal lobe. Although aphasic patients activated homologous areas in the right temporal lobe, such activation was not correlated with comprehension performance. Rather, patients with better comprehension exhibited increased activity in dorsal fronto-parietal regions. Correlations between performance and dorsal network activity occurred bilaterally during perception of sentences, and in the right hemisphere during a post-sentence memory delay. These results suggest that effortful reprocessing of perceived sentences in short-term memory can support improved comprehension in aphasia, and that strategic recruitment of alternative networks, rather than homologous takeover, may account for some findings of right hemisphere language activation in aphasia.

Error reduction therapy in reducing struggle and grope behaviours in apraxia of speech.

We report an intervention study focused on the speech production difficulties present in acquired apraxia of speech (AOS). The intervention was a self-administered computer therapy that targeted whole word production and incorporated error reduction strategies. The effectiveness of the therapy was contrasted to that of a visuospatial sham computer program, and performance across treated words, and two sets of matched words, was assessed. Two groups of participants completed the study which employed a two-phase cross-over treatment design. Participants were randomly assigned to a speech first or sham first condition. Treatments were administered for six weeks, with a four week rest between interventions. Participants were assessed five times in total; twice at baseline, once following each of the intervention phases, and once following a lapse of eight weeks after the end of the second phase of intervention. The occurrence of accurate word production and speech characterised by struggle and groping behaviours was recorded on a repetition task. Participants showed significant gains in speech accuracy and fluency, and reductions in articulatory groping and struggle behaviours following the use of the speech program. These gains were largely maintained once the therapy was withdrawn.

Efficacy and safety of dutasteride in patients with spinal and bulbar muscular atrophy: a randomised placebo-controlled trial.

BACKGROUND: Spinal and bulbar muscular atrophy (SBMA) is caused by polyglutamine expansion in the androgen receptor, which results in ligand-dependent toxicity. Animal models have a neuromuscular deficit that is mitigated by androgen-reducing treatment. We aimed to assess the efficacy and safety of the 5α-reductase inhibitor dutasteride in patients with SBMA, and to identify outcome measures for use in future studies of the disease. METHODS: We undertook a randomised, double-blind, placebo-controlled, single-site clinical trial in ambulatory, symptomatic men with genetically confirmed SBMA. Participants were assigned by random number table to receive dutasteride (0·5 mg per day) or placebo orally for 24 months. Patients and investigators were masked to treatment allocation. The primary outcome measure was quantitative muscle assessment (QMA). The final efficacy analysis included all patients who were compliant with study treatment at 24 months. This trial was registered with ClinicalTrials.gov, NCT00303446. FINDINGS: 50 men were randomly assigned to treatment groups (25 dutasteride, 25 placebo), and 44 were included in the efficacy analysis (21 dutasteride, 23 placebo). At 24 months, the placebo group showed a decrease of 4·5% (-0·30 kg/kg) from baseline in weight-scaled muscle strength as indicated by QMA, and the dutasteride group had an increase in strength of 1·3% (0·14 kg/kg); the difference between groups (5·8%, 95% CI -5·9 to 17·6; p=0·28) was not significant. Prespecified secondary outcome measures of creatine kinase, muscle strength and function, motor nerve conduction, activities of daily living, and erectile function did not show a significant difference between the study groups in change from baseline. Quality of life, as measured by the physical component summary of the Medical Outcomes Study 36-item Short Form version 2, favoured dutasteride (change in score from baseline: placebo, -3·6%, vs dutasteride, 2·1%; p=0·01), whereas the mental component summary favoured placebo (3·3%vs -3·2%; p=0·03). The dutasteride group had fewer patients reporting falls than did the placebo group (9 vs 16; p=0·048); there were no other significant differences in reported adverse events. INTERPRETATION: Our study did not show a significant effect of dutasteride on the progression of muscle weakness in SBMA, although there were secondary indications of both positive and negative effects compared with placebo. A longer trial duration or larger number of patients might be needed to show an effect on disease progression. Performance testing, QMA, and quality of life measures were identified as potentially useful endpoints for future therapeutic trials.

Naftifine: a review.

BACKGROUND: Naftifine is a topical allylamine that is effective and safe in the management of superficial dermatomycoses. Naftifine is fungicidal in vitro against a broad spectrum of dermatophyte fungi and provides good activity against Candida and Aspergillus species. It is also effective against gram-negative and gram-positive bacteria. OBJECTIVE: To provide a review of the pharmacologic properties and clinical efficacy of topical naftifine preparations. METHODS: A review of the medical literature was performed using PubMed (1965-2006) using the search term "naftifine." All available English-language articles discussing the pharmacology and clinical use of naftifine were reviewed for the article. RESULTS: Naftifine causes interruption of fungal ergosterol synthesis and accumulation of squalene in fungal organisms. Naftifine also has demonstrated anti-inflammatory properties such as a reduction in superoxide production and a reduction in polymorphonuclear leukocyte chemotaxis/endothelial adhesion. Naftifine has shown good efficacy and safety for a variety of conditions and is a useful treatment that provides both antifungal action and relief of inflammatory signs and symptoms. Few adverse events have been noted with naftifine use, the most frequent being mild and transient burning, stinging, or itching in the application area. CONCLUSION: Naftifine remains a reliable multifunctional agent for a variety of superficial infections.

Dermatophytosis: the management of fungal infections.

Dermatophytosis is an infection of the hair, skin, or nails caused by a dermatophyte, which is most commonly of the Trichophyton genus and less commonly of the Microsporum or Epidermophyton genera. Tinea capitis, tinea pedis, and onychomycosis are common dermatologic diseases that may result from such an infection. The treatment of fungal infections caused by a dermatophyte has been successful when treated with oral or topical antifungal agents. Terbinafine, itraconazole, and fluconazole are oral antimycotics that are effective in the treatment of superficial mycoses, although, depending on the severity of the infection, a topical antifungal may be sufficient.

The use of terbinafine in the treatment of onychomycosis in adults and special populations: a review of the evidence.

Terbinafine is an allylamine with fungicidal activity, first approved for the treatment of onychomycosis in the United Kingdom in the early 1990s, and in the US in 1996. Terbinafine is the most frequently prescribed oral antifungal agent in the US and Canada for onychomycosis. Its efficacy and safety in dermatophyte toenail onychomycosis in adults has been established in many studies. In fact, 18 randomized controlled trials have shown terbinafine to be highly effective, with a meta-average for mycological cure of 76% +/- 3% (mean +/- standard error). In large surveillance studies, terbinafine exhibited excellent safety profiles consistent with results obtained in pivotal studies. Additionally, terbinafine has been reported to be superior to both itraconazole and fluconazole in comparative studies in the treatment of dermatophyte toenail onychomycosis. Recent studies have reported terbinafine to be more cost effective than griseofulvin, fluconazole, or itraconazole. Terbinafine has also been used to treat onychomycosis effectively and safely in special patient populations, such as children, the elderly, immunocompromised patients, diabetics, and those with Down syndrome. Terbinafine should therefore be considered for the management of onychomycosis in adults based on its effectiveness, broad spectrum, fungicidal nature, established safety profile, and very low occurrence of drug interactions. Furthermore, the data support the use of terbinafine to treat dermatophyte onychomycosis in children and the elderly.

Optimal management of fungal infections of the skin, hair, and nails.

Superficial fungal infections are chronic and recurring conditions. Tinea capitis is a scalp infection, primarily affecting prepubescent children. Ringworm infections, such as tinea corporis and tinea cruris, involve the glabrous skin. Tinea nigra is a rare mycotic infection that may be related to travel abroad. Piedra, black or white, is limited to the hair shaft without involvement of the adjacent skin. Pityriasis (tinea) versicolor and seborrheic dermatitis are dermatoses associated with yeasts of the genus Malassezia that affect the lipid-rich areas of the body. The taxonomy of the Malassezia yeasts has been revised to include nine species, eight of which have been recovered from humans. Tinea pedis, an infection of the feet and toes, is one of the most common forms of dermatophytosis. Onychomycosis is a fungal infection affecting the nail bed and nail plate; it may be chronic and can be difficult to treat. In instances where the superficial fungal infection is severe or chronic, an oral antifungal agent should be considered. Terbinafine, itraconazole, and fluconazole are oral antifungals that are effective in the treatment of superficial mycoses.

Onychomycosis: classification and diagnosis.

Onychomycosis is a common infection of the nail predominantly caused by anthropophilic dermatophytes, and to a lesser extent by yeasts (Candida species) and non-dermatophyte molds. The treatment of onychomycosis is dependent on several variables, including the type of onychomycosis and the causative organism. Various techniques have been used to accurately diagnose onychomycosis, with microscopy and culture being used most frequently. Histological examination of the distal nail plate can aid in confirming the presence of invasive nail disease, but histological examination should not be limited to the nail plate as it may also be helpful in diagnosing subungual onychomycosis. Nucleic acid-based identification techniques may also be valuable when diagnosing onychomycosis; however, multiple steps may be necessary to determine the causative species. Confocal microscopy may also be a fast and reliable method of diagnosing onychomycosis, though it has very limited ability to distinguish between dermatophyte and mold infections. Prior to treatment an accurate diagnosis can provide guidance about the choice of antifungal agent, especially since the causative organism may vary in its response to the antifungal therapies available.

Treatment of onychomycosis: pros and cons of antifungal agents.

BACKGROUND: Antifungal agents are beneficial in the treatment of onychomycosis in the general population, as well as in children, the elderly, and immunocompromised individuals. Special patient populations can be more difficult to treat due to such factors as drug interactions with concomitant medications, adverse events, and poor compliance. In addition, there is limited information about the use of antifungal agents in special populations, e.g., children. OBJECTIVE: The pros and cons of oral and topical antifungal agents are discussed, with focus on special patient populations. METHODS: We searched MedLine (1966 to April 2003) for clinical studies evaluating the efficacy of oral and topical antifungal agents to treat onychomycosis. The key words used in conjunction with "onychomycosis" include: "terbinafine," "itraconazole," "fluconazole," "amorolfine nail lacquer," "ciclopirox nail lacquer," "HIV," "transplant patients," "diabetes," "children," and "elderly." Studies were excluded if published in a language other than English. RESULTS: Studies have shown that antifungal agents can be of benefit in treating the elderly, children, and immunocompromised individuals (e.g., transplant patients, Down's patients, HIV patients, and diabetics) with onychomycosis. CONCLUSION: The treatment modality of onychomycosis in special patient populations should take into account the clinical presentation of the onychomycosis, the causative organism, patient and physician preference, the concomitant medications that the patient is on, and the potential for adverse events for that patient if antifungal therapy is undertaken.

Superficial fungal infections: an update on pityriasis versicolor, seborrheic dermatitis, tinea capitis, and onychomycosis.

The recent advances in pityriasis versicolor, seborrheic dermatitis, tinea capitis and onychomycosis are reviewed. Some highlighted points include the new classification of Malassezia species, and the association of Malassezia species with seborrheic dermatitis. The use of terbinafine, fluconazole, and itraconazole for the treatment of tinea capitis is discussed. The management of onychomycosis, highlighting the high efficacy rates obtained with terbinafine when used to treat dermatophyte toenail onychomycosis, is discussed. The use of combination therapies in some circumstances to maximize cure rates is reviewed.

The use of oral antifungal agents to treat onychomycosis.

Onychomycosis has been treated for years with oral antifungal agents, and more recently in the United States with a topical nail lacquer. Griseofulvin was the first significant oral agent available to manage onychomycosis. The introduction of the azoles (ketoconazole, itraconazole, and fluconazole) and the allylamine, terbinafine, led to improved cure rates and a broad spectrum of activity. Pharmacokinetic studies have shown that the newer oral agents penetrate the nail within approximately one to two weeks after the start of therapy and remain for several months after the end of treatment. This article reviews the oral antifungal agents used to treat onychomycosis.

The use of topical therapies to treat onychomycosis.

The management of onychomycosis using topical agents has improved with the introduction of ciclopirox and amorolfine nail lacquers; other topical agents may be less effective. The combination of a nail lacquer with an oral antifungal agent may further improve efficacy rates in certain clinical presentations (eg, among those individuals with severe onychomycosis). Topical agents have a favorable adverse events profile. Further studies are required on the treatment of onychomycosis with nail lacquers.

How to improve cure rates for the management of onychomycosis.

To improve the treatment of onychomycosis clinicians need to identify correctly the causative organism, choose a therapy that is effective against the pathogen, and take into consideration the pharmacokinetics (eg, bioavailability, drug interactions) of the oral agent. In addition, variations of the standard regimens may need to be considered (ie, booster or supplemental therapy). To reduce the recurrence of onychomycosis, once mycologic cure has been achieved, clinicians should educate their patients about proper foot care. Familiarity with the symptoms and signs of tinea pedis and onychomycosis may enable patients to seek appropriate care when the disease is at an early stage.

Photodynamic therapy and topical aminolevulinic acid: an overview.

Photodynamic therapy is a non-invasive technique used in the treatment of skin diseases which has various advantages, one being the ability to localize treatment to the area being treated, which is common among most photosensitizers. Aminolevulinic acid is a prodrug that is metabolized intracellularly to form the photosensitizing molecule protoporphyrin IX (PpIX). When PpIX is activated by light, cytotoxic reactive oxygen species and free radicals are generated. This phototoxic effect may cause malignant and non-malignant hyperproliferative tissue to be destroyed, to decrease in size, and to eventually disappear. The application of topical aminolevulinic acid 20% followed by the use of a blue light photodynamic therapy illuminator is indicated in the US for the treatment of non-hyperkeratotic actinic keratoses of the face or scalp. There are data suggesting that aminolevulinic acid/photodynamic therapy may also be beneficial in acne vulgaris, verrucae, psoriasis, mycosis fungoides, and human papillomavirus. This treatment modality has also proven effective in the management of skin cancer such as, Bowen disease and basal cell carcinoma. Further experience in the use of photodynamic therapy will help define its utility in the management of actinic keratosis and other dermatoses.

Onychomycosis: quality of studies.

OBJECTIVE: The quality of original clinical trial publications pertaining to the use of oral antifungal agents to treat onychomycosis was evaluated using predetermined criteria. METHODS: The list of studies included in this analysis was determined by conducting a search in Medline. For each clinical trial, two independent reviewers each determined a composite score by evaluating a list of criteria that were felt to represent a good study, for example, randomization and blinding, prior sample size calculated, and treatment regimen clearly explained. A citation count was performed to determine whether higher-quality papers were cited more often than lower-quality papers. RESULTS: Forty-five studies were included in this quality analysis of study design. Of these, 27 were considered to be "high quality" (score greater than or equal to 11 out of 20). A significant correlation coefficient of 0.997 was found between the two reviewers (P < 0.00001). Higher-quality papers were cited significantly more often than lower-quality papers (P = 0.03). CONCLUSION: The scale that we use to evaluate the quality of onychomycosis studies has high interrater reliability. According to this scale, many published studies (18 out of 45) pertaining to treatments for onychomycosis do not meet the criteria required to be considered "high quality."

Non-dermatophyte onychomycosis.

Non-dermatophyte organisms are becoming increasingly prevalent in onychomycosis. This apparent emergence might be an artifact of improved diagnostic techniques and increased awareness that these fungi are potential etiologic agents. It is important to bear in mind that all isolated organisms should be evaluated as potential pathogens when diagnosing fungal infections, especially given the increasing use of immunosuppressive drugs and the increasing numbers of chronically immunocompromised individuals. While many patients with non-dermatophyte mold onychomycosis will respond to oral or topical antifungal therapy, poor or incomplete response might still be expected in some patients.