BACKGROUND: The SCAN genitourinary cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for the management of advanced castrate-resistant prostate cancer.
METHODS: The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting.
RESULTS: Five international guidelines were evaluated- those developed by the National Comprehensive Cancer Network (2014), the European Society of Medical Oncology (2013), the American Urological Association (2013), the National Institute of Health and Clinical Excellence (2014) and the American Society of Clinical Oncology and Cancer Care Ontario (2014). Recommendations on the management of advanced castrate-resistant prostate cancer were developed.
CONCLUSIONS: These adapted guidelines form the SCAN Guidelines 2015 for the management of advanced castrate-resistant prostate cancer.

This document summarizes current knowledge about diagnosis and treatment of candidiasis affecting the skin and oral mucosa. Several clinical forms of mucocutaneous candidiasis are distinguished depending on a patient\'s age and infected site, e.g. Candida intertrigo, erythema mycoticum infantile, erosio interdigitalis blastomycetica, candidal paronychia and onychia, Candida onychomycosis, and oral candidiasis. The diagnosis of candidiasis is confirmed by observation of mycelial forms on microscopic examination. Since Candida yeasts (especially C. albicans) are normal inhabitants of the skin and oral mucosa, it must always be noted that positive culture does not always indicate the presence of candidal infection. The pathogenicity of Candida species is relatively low, and some special conditions are required for tissue invasion by the fungus. Predisposing factors, such as disturbances of the cutaneous and mucosal microenvironment and systemic or local immunosuppression, should be checked in patients with recurrent infection. Therapy for cutaneous candidiasis is dominated by topical antifungal agents. Azole antifungal cream (e.g., bifonazole, ketoconazole, neticonazole hydrochloride, lanoconazole and luliconazole) is most effective. Terbinafine hydrochloride and amorolfine hydrochloride are also useful. Cutaneous candidiasis usually requires a shorter duration of topical treatment (1-2 weeks) than superficial dermatophyte infections. For candidal paronychia and onychomycosis, oral therapy with itraconazole is recommended. The daily dose of itraconazole should be taken for several months, while its pulse therapy for candidiasis is not approved in Japan. Itraconazole oral solution is commonly used for oral candidiasis, and miconazole gel is also effective.

We performed a 28-day repeated-dose toxicity study of ketoconazole, a widely used an antimycotic drug, based on the draft protocol of the \"Enhanced OECD Test Guideline 407\" (Enhanced TG407) to investigate whether ketoconazole has endocrine-mediated properties according to this assay. Seven-week-old SD rats were administered with ketoconazole daily by oral gavage at doses of 0, 6.25, 25 or 100 mg kg(-1) day(-1) for at least 28 days. The ketoconazole-treated male rats showed reduction of epididymis and accessory sex organ weights, spermatid retention in the seminiferous tubules, decrease of testosterone and increases of estradiol, luteinizing hormone (LH) and follicular stimulating hormone (FSH). A prolongation of the estrous cycle and increases of estradiol, LH and FSH were observed in the treated female rats. Thyroxin and triiodothyronine were decreased and thyroid-stimulating hormone was increased in both sexes; however, there were no compound-related microscopic lesions in the thyroid gland or changes in the thyroid weight. The endocrine-related effects of ketoconazole could be detected by the parameters examined in the present study based on the Organization for Economic Cooperation and Development (OECD) protocol, suggesting that the Enhanced TG407 protocol should be a suitable screening test for detection of endocrine-mediated effects of chemicals.

暂无摘要。

OBJECTIVE: The purpose of this study was to develop, implement, and evaluate a practice guideline using ketoconazole for the prevention of the adult respiratory distress syndrome (ARDS) in critically ill patients.
METHODS: In hospital A (study hospital), we developed a guideline for ketoconazole prophylaxis in patients at high risk of ARDS using evidence from two randomized trials. We prospectively implemented the guideline using intensive care unit (ICU) teaching sessions, in-services, informational posters, and patient-specific individual audit and feedback. ICU caregivers in hospital B (concurrent control hospital) did not participate in the guideline development or implementation and were unaware of the conduct of the study.
RESULTS: Patients at risk of ARDS were similar in hospitals A and B. Implementation of the guideline was associated with a significantly higher use of ketoconazole use for ARDS prevention (P < .0001) and a significantly lower rate of ARDS (P < .05) in hospital A compared with hospital B. Mortality, duration of ventilation, and ICU stay were similar.
CONCLUSIONS: Development and implementation of a prophylactic ketoconazole practice guideline for ICU patients at high risk of ARDS was associated with a higher prescription of ketoconazole and a lower rate of ARDS in the study hospital than in the control hospital.

Ketoconazole and itraconazole were tested in a multilaboratory study to establish quality control (QC) guidelines for yeast antifungal susceptibility testing. Two isolates that had been previously identified as QC isolates for amphotericin B, fluconazole, and flucytosine (Candida parapsilosis ATCC 22019 and Candida krusei ATCC 6258) were tested in accordance with the National Committee for Clinical Laboratory Standards M27-P guidelines. Each isolate was tested 20 times with the two antifungal agents in the five laboratories by using a lot of RPMI 1640 unique to each laboratory as well as a lot common to all five laboratories, thus generating 200 MICs per drug per organism. Overall, 96 to 99% of the MICs for each drug fell within the desired 3-log2 dilution range (mode +/- 1 log2 dilution). By using these data, 3-log2 dilution QC ranges encompassing 98% of the observed MICs for three of the organism-drug combinations and 94% of the observed MICs for the fourth combination were established. These QC ranges are 0.064 to 0.25 micrograms/ml for both ketoconazole and itraconazole against C. parapsilosis ATCC 22019 and 0.125 to 0.5 micrograms/ml for both ketoconazole and itraconazole against C. krusei ATCC 6258.

The imidazoles have been appreciated for approximately fifteen years as a family of antifungals. Most derivatives, like the protype compounds, miconazole and clotrimazole, are effective only in a topical dose form. The topical imidazoles are generally thought to be superior to other topical antifungals. The first orally available imidazole, ketoconazole has ushered in a new era of potent, oral, broad-spectrum antifungal therapy. The imidazoles as a class are the treatment of choice for four dermatophyte infection syndromes. They are the preferred alternative therapy in another six syndromes. There is insufficient data to recommend one topical azole over the other. The topicals are inadequate for control of six clinical-anatomical infection syndromes. Griseofulvin remains the standard oral therapy in all situations except chronic, extensive dermatophytosis, where ketoconazole has proven to be more efficacious. The recognition of potential significant adverse effects, namely an idiopathic hepatitis and dose-dependent adrenal and testicular dysfunction have reduced ketoconazole\'s potential role in the dermatophytoses. Ketoconazole is a useful alternative to griseofulvin when oral therapy is required and the causative organism is insensitive to griseofulvin, or infection fails to respond to griseofulvin, or griseofulvin is contraindicated due to allergy, photosensitivity, porphyrinuria, intolerance, etc.