Onychomycosis in Denmark: prevalence of fungal nail infection in general practice

The study was initiated in order to get knowledge of the frequency of onychomycosis in patients visiting general practitioners in Denmark. A study design was using a display showing photos of abnormal nails including fungal infection, a clinical examination and a questionnaire. The practitioners obtained nail material. Direct microscopy and culture as well as histopathology, were carried out blindly in two different mycological laboratories. A number of 8546 patients were seen during the 6 months of the study, 5755 (67.3%) took part in the investigation. Clinical abnormal nails were observed in 948 (16.5%) patients, 52% males and 48% females, aged 18-92, mean 55 years old. Onychomycosis caused by dermatophytes were found in 238 (4.1%) and by Candida albicans in 45 (0.8%). Trichosporon cutaneum and Scopulariopsis brevicaulis were isolated each in 15 cases as single cultures. Onychomycosis, was typically seen in toenails as the distal-lateral type in males more than 40 years old. Predisposing factors were familiar dermatophytosis (22%), trauma (16.9%), diabetes mellitus (6.7%) and peripheral circulatory insufficiency (5.9%).     

Onychomycosis in Tehran: mycological study of 504 patients

Onychomycosis is a common nail disorder resulting from the invasion of the nail plate by a dermatophyte, yeast or mould species and gives rise to some diverse clinical presentations. The purpose of the present study was to isolate and identify the causative fungi of onychomycosis in the population of Tehran, Iran. Nail samples from 504 patients with prediagnosis of onychomycosis during 2005 were examined both by direct microscopical observation of fungal elements in KOH preparations and in culture for the identification of the causative agent. All samples were inoculated on (i) Sabouraud dextrose agar (SDA, Merck), (ii) SDA with 5% chloramphenicol and cycloheximide in duplicate for dermatophyte and (iii) SDA with 5% chloramphenicol in triplicate for mould isolation. The criteria for the diagnosis of onychomycosis caused by non‐dermatophytic moulds were based on microscopical observation of fungal elements, growth of the same mould in all triplicate culture and no growth of a dermatophyte or yeast in all the cultures. Of 504 cases examined, 216 (42.8%) were mycologically proven cases of onychomycosis (144 fingernails, 72 toenails). Among the positive results, dermatophytes were diagnosed in 46 (21.3%), yeasts in 129 (59.7%) and non‐dermatophytic moulds in 41 (19%). Trichophyton mentagrophytes was the most common causative agent (n = 22), followed by Trichophyton rubrum (n = 13), Candida albicans (n = 42), Candida spp. (n = 56) and Aspergillus spp. (n = 21). Nearly half of the clinically suspected fungal nail infections are onychomycosis and yeast is responsible for most of the infections in Iran.     

Efficacy of 4 weeks topical bifonazole treatment for onychomycosis after nail ablation with 40% urea: a double‐blind,randomized, placebo‐controlled multicenter study

Onychomycosis is a common fungal infection most often affecting the toenails. If untreated, it can cause discomfort sufficient to reduce quality of life. To evaluate efficacy and safety of bifonazole cream vs. placebo in onychomycosis treatment after non‐surgical nail ablation with urea paste. Fifty‐one study centres randomized 692 subjects with mild‐to‐moderate onychomycosis to receive bifonazole 1% cream or placebo for 4 weeks following non‐surgical nail ablation with urea 40% paste over 2–4 weeks. Efficacy of the two phase treatment was evaluated by overall cure of the target nail comprising clinical and mycological cure 2 weeks, 3 and 6 months after end of treatment. At 2 weeks (primary endpoint), overall cure rate was superior in bifonazole‐treated group (54.8% vs. 42.2% for placebo; P = 0.0024). The clinical cure rate was high in both treatment groups (86.6% bifonazole vs. 82.8% placebo), but proportion with mycological cure was higher with bifonazole treatment (64.5%) vs. placebo treatment 49.0%, (P = 0.0001). We observed higher early overall cure rate with 4 weeks topical bifonazole compared with placebo after removal of infected nail parts with urea. This two stage treatment was well tolerated and offers an additional option in topical onychomycosis therapy.     

Morphopathological aspects of healthy nails and nails affected by onychomycosis

Patients of onychomycosis are common in the dermatology practice. Contemporary morphology creates opportunities to study the functional units of the nail when such infections occur from morphopathological point of view. There were 22 nails biopsies from onychomycosis patients taken for the research of morphopathological changes in the thickened nail plate affected by onychomycosis. Samples of cadaverous' nails were used as a control material. The material was stained with haematoxylin and eosin and immunohistochemical methods. Terminal deoxynucleotidyl transferase dUTP nick end labelling reaction and periodic acid‐Schiff reaction were also performed. We found patchy hypertrophy in the granulose layer of the epidermis, with focal acanthosis. In the horn layer, we identified nests of parakeratosis of various sizes, with incorporations of homogenous and eosinophil masses. We found high levels of interleukin 6 and interleukin 10 positive cells in the nail bed and in the bloodstream. Interleukin 1, however, was not a part of any of the functional units of any of the nails. Significant amount of fibres containing human beta defensin‐2 were found in the bed and plate of the nail. Therefore one can conclude that as regards the nails affected by onychomycosis, the most effective morphopathogenical processes include cytokine and defensin excretion occurrence in the nail bed.     

Comparison of user‐friendliness and treatment cost of Loceryl® vs. Ciclopoli® – a patient's perspective

Topical monotherapy is a valid therapeutic approach in onychomycosis. Due to its lengthy course and its non‐reimbursed product status, cost and compliance are important issues and non‐pharmacological properties such as over‐the‐counter price and ease of use should be considered when deciding which product to recommend. We investigated surrogate parameters for patient‐friendliness and treatment cost in Germany in a questionnaire‐based prospective, comparative, intra‐individual, open‐label trial of the two common topical antifungal nail lacquers Loceryl^® (amorolfine 5%) and Ciclopoli^® (ciclopirox 8%) in eight patients with clinically diagnosed onychomycosis. The 2.5 ml bottle of Loceryl^® covered a treatment period of 308 days, resulting in treatment costs of €0.10 per day in comparison to the 3.3 ml bottle of Ciclopoli^®, covering 127 days at €0.21 per day, given once‐daily application for Ciclopoli^® and once‐weekly application for Loceryl^® in accordance with regulatory approval. Six out of eight patients favoured the Loceryl^® treatment regimen. Furthermore, four out of eight patients found Loceryl^® easier to apply, whereas three preferred Ciclopoli^®. In total, seven out of eight stated a clear preference for Loceryl^® over Ciclopoli^®. Loceryl^® therapy is less expensive and less time‐consuming. The therapeutic period that can be covered is longer and more patients stated a clear preference for Loceryl^® in comparison to Ciclopoli^®. The differences are statistically significant, underlining probable clinical relevance.     

Sporicidal effect of amorolfine and other antimycotics used in the therapy of fungal nail infections

Although topical antifungal therapies for treating onychomycosis are available, the cure rate is unsatisfactorily low with a simultaneously high risk of recurrence. One reason might be the formation of dormant fungal cells by the pathogen, known as spores, which can survive in the affected nail keratin, thereby evading the effect of antifungal drugs. In this in vitro study, the ability of amorolfine and four other antimycotics (ciclopirox, bifonazole, terbinafine and fluconazole) to kill microconidia of the dermatophyte Trichophyton rubrum, chlamydospores of the dermatophyte Epidermophyton floccosum and blastospores of the yeast Candida albicans was extensively studied as these fungi occur predominantly in onychomycosis. The effectiveness of all five antimycotics depended on the drug concentration and the incubation time: a concentration of 10–1000 times the minimum inhibitory concentration against growing hyphae cells is needed to exert a sporicidal action. Amorolfine and ciclopirox showed the same sporicidal efficacy and kinetics for all three varieties of spores. Both were more effective than fluconazole and bifonazole against microconidia and chlamydospores as well as slightly more potent against chlamydospores and blastospores than terbinafine after 4 days of incubation and at concentrations of ≥10 μg ml^?1. Finally, sporicidal activity on the tested strains was demonstrated for all five different antimycotics used for onychomycosis treatment.     

A population-based audit of ethnicity and breast cancer risk in one general practice catchment area in North London,UK: implications for practice

Objectives

To conduct a pilot population-based study within a general practice catchment area to determine whether the incidence of breast cancer was increased in the Ashkenazi population.

Design

Population-based cohort study.

Setting

A single general practice catchment area in North London.

Participants

1947 women over the age of 16 who responded to a questionnaire about ethnicity and breast cancer.

Main outcome measures

Incidence of breast cancer, ethnicity.

Results

This study showed a 1.5-fold (95% CI 0.93–2.39) increase in breast cancer risk in the Ashkenazim compared with the non-Ashkenazi white population. The increased incidence was for both premenopausal and postmenopausal breast cancer (expected incidence pre:post is 1:4 whereas in the Ashkenazim it was 1:1; 51 and 52% of cases respectively). This increase was not shown in the Sephardim. Asians had a reduction in incidence (OR = 0.44; 95% CI 0.10–1.89). Results were adjusted for other risk factors for breast cancer.

Conclusion

This study showed a 1.5-fold increase in breast cancer rates in Ashkenazim compared with the non-Jewish white population when adjusted for age (i.e. corrections were made to allow comparison of age groups) and this is not observed in the Sephardic population. The proportion of premenopausal breast cancer was just over double that of the general population. This is the first general practice population-based study in the UK to address this issue and has implications for general practitioners who care for patients from the Ashkenazi community.

     

Determination of the efficacy of terbinafine hydrochloride nail solution in the topical treatment of dermatophytosis in a guinea pig model

Currently available topical antifungals are often not satisfactory for the treatment of nail infections, because of the inability to penetrate the nail plate. Terbinafine HCl nail solution is a novel antifungal formulation containing a nail penetration enhancer dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP HCl, trade name NexACT-88). In this study, we used a guinea pig model of Trichophyton mentagrophytes dermatophytosis and evaluated the clinical and mycological efficacy of different terbinafine HCl nail solutions (TNS) formulated with or without DDAIP HCl. Ciclopirox (8%) nail lacquer (Penlac), the only Food and Drug Administration approved topical treatment for onychomycosis, was used as a comparator. Following the IACUC Guidelines, the skin of male albino guinea pigs was abraded under anaesthesia. Each animal was infected with T. mentagrophytes ATCC 24953 (cell suspension containing 1 x 10(7) conidia). The experimental animals were divided into 11 groups (five animals per group) and tested with the following formulations: vehicle control, 0.5% DDAIP HCl, 1%, 5% and 10% TNS (without DDAIP HCl), 1% TNS with 0.5%, 2.5% and 5.0% DDAIP HCl, 5% and 10% TNS with 0.5% DDAIP HCl, 8% ciclopirox nail lacquer and an untreated control group. Evaluation of clinical and mycological efficacy was performed 72 h after completion of a 7-day treatment regimen. Skin biopsy samples were processed for histopathological examination. The infected untreated control guinea pigs showed patches of hair loss and ulcerated or scaly skin and fungal invasion of hair roots. The vehicle and 0.5% DDAIP HCl treated groups showed minimal clinical efficacy (only 11% and 5%, respectively). In contrast, all three concentrations of TNS (1%, 5% and 10% terbinafine HCl) formulated with or without 0.5% DDAIP HCl showed 100% mycological efficacy by the hair root invasion test. Clinical efficacy of the 5% and 10% TNS improved with addition of 0.5% DDAIP HCl (47.4% and 73.8% vs. 68.4% and 89.5%, respectively). In addition, no fungal elements were detected in the treated guinea pig skin. All formulations of TNS resulted in a higher clinical and mycological efficacy compared with the 8% ciclopirox nail lacquer (P = 0.0444). In conclusion, TNS containing 1%, 5% and 10% terbinafine HCl formulated with and without DDAIP HCl demonstrated high antifungal efficacy in experimental dermatophytosis. Addition of 0.5% DDAIP HCl to 5% and 10% TNS significantly enhanced the clinical and mycological efficacy of these formulations which were superior compared with the 8% ciclopirox nail lacquer. Evaluation of the 1%, 5% and 10% TNS in clinical trials for the treatment of dermatophytosis and onychomycosis is warranted.     

Retrospective study of onychomycosis in Italy: 1985-2000

Cases of onychomycosis diagnosed by mycological examination in three mycology units (Florence, Siena and Milan) of central and northern Italy over the 15-year period, 1985-2000, were studied retrospectively. The number of cases was 4046 (1952 women, 2094 men). Dermatophytes were isolated in 2859, yeasts in 655 and moulds in 532 cases. The most frequent dermatophyte was Trichophyton rubrum (87%), followed by T. mentagrophytes var. interdigitale (10%). Candida albicans (93.2%) was the prevalent yeast. Moulds were mainly Scopulariopsis brevicaulis (48.6%) and Aspergillus spp. (25.2%). Dermatophytes and moulds most commonly infected the toenails, yeasts the fingernails.     

Impact of investigations in general practice on timeliness of referral for patients subsequently diagnosed with cancer: analysis of national primary care audit data

Background:

For patients with symptoms of possible cancer who do not fulfil the criteria for urgent referral, initial investigation in primary care has been advocated in the United Kingdom and supported by additional resources. The consequence of this strategy for the timeliness of diagnosis is unknown.

Methods:

We analysed data from the English National Audit of Cancer Diagnosis in Primary Care on patients with lung (1494), colorectal (2111), stomach (246), oesophagus (513), pancreas (327), and ovarian (345) cancer relating to the ordering of investigations by the General Practitioner and their nature. Presenting symptoms were categorised according to National Institute for Health and Care Excellence (NICE) guidance on referral for suspected cancer. We used linear regression to estimate the mean difference in primary-care interval by cancer, after adjustment for age, gender, and the symptomatic presentation category.

Results:

Primary-care investigations were undertaken in 3198/5036 (64%) of cases. The median primary-care interval was 16 days (IQR 5–45) for patients undergoing investigation and 0 days (IQR 0–10) for those not investigated. Among patients whose symptoms mandated urgent referral to secondary care according to NICE guidelines, between 37% (oesophagus) and 75% (pancreas) were first investigated in primary care. In multivariable linear regression analyses stratified by cancer site, adjustment for age, sex, and NICE referral category explained little of the observed prolongation associated with investigation.

Interpretation:

For six specified cancers, investigation in primary care was associated with later referral for specialist assessment. This effect was independent of the nature of symptoms. Some patients for whom urgent referral is mandated by NICE guidance are nevertheless investigated before referral. Reducing the intervals between test order, test performance, and reporting can help reduce the prolongation of primary-care intervals associated with investigation use. Alternative models of assessment should be considered.     

Treatment of dermatophyte onychomycosis with three pulses of terbinafine (500 mg day for a week)

We assessed the safety and efficacy of pulse therapy with terbinafine tablets in 55 patients with dermatophytic onychomycosis. One pulse consisted of oral terbinafine tablets (500 mg day⁻¹) given for 1 week usually followed by a 3-week interval. This regimen was repeated twice. Topical 1% terbinafine cream was applied daily. Efficacy was assessed based on both clinical and mycological examinations 1 year after treatment initiation. We observed a complete cure in 41 patients (74.5%), marked improved in three patients (5.6%), slight improvement in three patients (5.6%) and drop out in six patients (10.7%). Two patients (3.6%) discontinued terbinafine because of gastrointestinal disturbance (one patient) and drug-induced eruption (one patient). No patient had abnormal laboratory findings, including liver function tests. In summary, a regimen of three pulses of terbinafine therapy given daily for 1 week in combination with topical application of terbinafine cream appears to be safe and effective in treating dermatophytic onychomycosis and offers advantages in convenience and cost-effectiveness compared with continuous dosing.     

Frequency,type and treatment of fungal pathogens in toenail onychomycosis in the central Alpine region of South Tyrol,northern Italy – a 10‐year retrospective study from 2004 to 2013

Onychomycosis is one of the most common dermatological diseases, primarily caused by dermatophytes, and sometimes, also by yeast and moulds. This study aims to clarify the frequency of isolated pathogens from mycotic toenails in the reference centre of the central Alpine mountain region of South Tyrol, northern Italy. Age and gender differences, types of pathogens and initial therapy used were also investigated. This is a retrospective study from 2004 to 2013 on the files of all patients with suspected onychomycosis in whom a cultural pathogen detection was performed. A total of 1565 patients were studied (943 women; 622 men), with a median age of 55 years. Fungal pathogens could be detected by culture in 49.5%. Significantly more pathogens could be grown in men (63.8%) than in women (39.9%, P < 0.0001). The most common pathogens grown were dermatophytes (53.3%), especially T. rubrum and T. interdigitale, followed by moulds (24.7%) and yeast (22%). Therapies prescribed were topical in 64.2% and systemic in 35.8% of the cases. Topical treatment was more frequent in older patients (P < 0.05). In northern Italy, dermatophytes are the most common causative agents for onychomycosis. Fungal pathogens were more commonly found in men than in women and topical treatment was more frequent in older patients.     

Consensus approaches to best practice management of gastrointestinal stromal tumors

Gastrointestinal stromal tumors are rare mesenchymal tumors of the gastrointestinal tract. Progress in diagnosis has led to increased recognition of this disease, and the availability of effective, molecularly targeted therapy has revolutionised its management. Treatment of metastatic gastrointestinal stromal tumors with imatinib has led to unprecedented improvements in progression free and overall survival and there are ongoing investigations into the optimal pre‐operative and adjuvant use of imatinib. Second‐line sunitinib is now available for patients who develop resistance to imatinib, and third‐ and fourth‐line therapies are being investigated in clinical trials. In this ever‐changing environment, evidence from controlled clinical trials and the authors' experience were used to comprehensively outline current best practice management of patients with gastrointestinal stromal tumors.     

One week pulse therapy with itraconazole (200 mg day−1) for onychomycosis. Evaluation of treatment results according to patient background

We investigated background factors of patients that affect the response of onycomycosis to pulse therapy with itraconazole. The regimen used in this study involved administering 200 mg of itraconazole orally on a daily basis for 1 week as one pulse, which is half of the normally recommended dose. The number of pulses was fixed at one per month, and altered in accordance with improvements in the infected nails and/or the patients' request. Patient background (n = 63) including sex, age, occupation, duration of the disease, site of lesion (fingernail, toenail), number of affected nails, clinical types, severity of thickening, presence or absence of pathogens, the presence or absence of underlying diseases such as adult onset diseases, turbidity of the target nails before therapy and the number and duration of pulses was investigated. The efficacy of the therapy was evaluated after 12 months. A complete cure was judged to have taken place if an entirely healthy nail plate re-grew in place of the diseased nail, whereas lack of success was defined as the persistence of lesions beyond the designated time period. The average number and duration of pulses were 4.7 +/- 3.2 times over 5.6 +/- 4.3 months, respectively. The rate of complete cure was 62%. Factors in the patients' background that were judged to have an influence on treatment results were the relative duration of the disease, the number of affected nails, and severity of thickening. With regard to the efficacy of the therapy in terms of the number and duration of pulses, 78% of 23 patients who were given pulse therapy two to six times during a course of 2 to 6 months achieved total cure.     

Adherence to best practice consensus guidelines for implant-based breast reconstruction: Results from the iBRA national practice questionnaire survey

Introduction

The 2008 National Mastectomy and Breast Reconstruction Audit demonstrated marked variation in the practice and outcomes of breast reconstruction in the UK. To standardise practice and improve outcomes for patients, the British professional associations developed best-practice guidelines with specific guidance for newer mesh-assisted implant-based techniques. We explored the degree of uptake of best-practice guidelines within units performing implant-based reconstruction (IBBR) as the first phase of the implant Breast Reconstruction Evaluation (iBRA) study.

Promoting best gynecologic oncology practice: a role for the Society of Gynecologic Oncologists of Canada

During March 30-April 1, 2005, the Society of Gynecologic Oncologists of Canada (GOC) and the Canadian Strategy for Cancer Control (CSCC) Clinical Practice Guidelines Action Group (CPG-AG) met to determine how GOC would like to influence practice in the care of women with gynecologic cancer.explore a collaborative model for developing and implementing evidence-based practice guidelines.investigate the utility of the cpg evaluation and adaptation cycle as a tool for selecting, adapting, and adopting guidelines.At the workshop meeting, 21 members of the GOC and the cpg-ag heard presentations from various Canadian guideline initiatives. As an example of adaptation and adoption processes, the AGREE (Appraisal of Guidelines for Research and Evaluation) tool was applied to guidelines in recurrent ovarian cancer, and the group explored their opportunity to use knowledge translation to influence the care of women with gynecologic cancer.The themes influencing practice are consistent with GOC's mandate. The future is expected to involve partnering with other groups to maximize scarce resources. Resources should be directed to facilitating implementation of existing guidelines rather than to developing new documents. The full spectrum of cancer care includes prevention, screening, diagnosis, primary treatment, follow-up, treatment of recurrent disease, and palliation. High-quality evidence is available in some areas, but gaps exist where guideline panels could provide guidance. Development of a pan-Canadian gynecologic oncology process could provide an opportunity to influence access to care at the political and policy levels.The GOC will develop linkages such that the toolbox available through CSCC-CPG-AG can be incorporated into future collaboration.     

Intermittent therapy with terbinafine and nail abrasion for dermatophyte toe onychomycosis: a pilot study

Onychomycosis constitutes up to 50% of all nail disorders. Toenails are generally affected, mostly due to dermatophytes. Terbinafine is the most potent antifungal agent in vitro against dermatophytes. There are few randomised controlled trials using a non‐continuous dose of terbinafine. The aim of this open‐label pilot study was to reduce the total drug amount, the collateral effects and, specially, the costs; albeit maintaining the same efficacy of the standard regimens. Compare the outcomes of two different intermittent regimens with the same total amount of the medication (42 tablets in 6 months). Forty‐one patients were divided into the following groups: terbinafine 250 mg day^?1, for 7 days, monthly or terbinafine 500 mg day^?1, once daily, for 7 days, every 2 months, both plus nail abrasion during 6 months. The efficacy was evaluated at months 6, 12 and 18 using the disease free nail criteria. Total cure = group I: eight patients (44.4%) and group II: eight patients (44.4%). Partial cure = group I: five patients (27.8%) and group II: four patients (22.2%). Treatment failure = group I: five patients (27.8%) and group II: three patients (16.7%). Recurrence = group I: zero patients (0.0%) and group II: three patients (16.7%). Two intermittent dosing regimens of terbinafine plus nail abrasion proved to be an alternative statistically effective, safe and with reduced drug costs for dermatophytes toenail onychomycosis.