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Notes: Background One of the most troublesome features of atopic dermatitis (AD) is its chronic relapsing nature, and there is a lack of published evidence on the best treatment strategy for long-term management of the disease. Objectives To compare an intermittent dosing regimen of fluticasone propionate (FP) cream 0·05% (twice per week) with its vehicle base in reducing the risk of relapse when added to regular daily emollient in adult and paediatric subjects with stabilized AD. Methods Subjects (aged 3 months to 65 years) with moderate or severe AD were enrolled into an open-label Stabilization Phase of up to 4 weeks on daily emollients plus FP twice daily. Those subjects who achieved ‘treatment success’ (Global Assessment Score ≤ 2, erythema, pruritus, and papulation/induration/oedema scores ≤ 1) entered the double-blind Maintenance Phase. They continued with regular emollients and were randomized at a 2 : 1 ratio to either intermittent FP or vehicle, once daily 4 days per week for 4 weeks followed by once daily 2 days per week for 16 weeks. Subjects who relapsed on intermittent FP were discontinued from the study. Those who did not relapse continued for an additional 24 weeks on intermittent dosing for safety monitoring. Results A total of 372 (247 paediatric, 125 adult) subjects were enrolled into the Stabilization Phase. Of these, 348 (231 children, 117 adults) were randomized into the Maintenance Phase. Analysis of the primary efficacy parameter showed that subjects receiving intermittent FP cream (twice per week), in addition to regular daily emollients in the Maintenance Phase, were 7·7 times less likely to have an AD relapse than subjects receiving intermittent vehicle cream/emollients [Mantel–Haenszel (MH) estimate of the odds ratio, 95% confidence interval (CI) 4·6, 12·8; P 〈 0·001]. Paediatric subjects were 8·1 times less likely to have an AD relapse (95% CI 4·3, 15·2; P 〈 0·001) and adult subjects were 7·0 times less likely to have an AD relapse (95% CI 3·0, 16·7; P 〈 0·001). For subjects receiving intermittent FP cream/emollient, the median time to relapse could not be estimated as the majority remained controlled at 20 weeks. For those receiving intermittent vehicle/emollient, the median time to relapse was 4·7 weeks. For paediatric and adult groups, this was 5·1 and 4·1 weeks, respectively. Median exposure to FP for all subjects was 337 days. There was only one study drug-related adverse event (acne) and there were no reports of skin thinning or atrophy associated with the use of FP cream in paediatric or adult subjects. Conclusions In paediatric and adult subjects, once stabilized with regular FP treatment, the risk of relapse of AD can be significantly reduced by extended intermittent dosing with FP cream in addition to regular emollient therapy.

Notes: Background  Onychomycosis is a common nail disease that is often chronic, difficult to eradicate, and has a tendency to recur. The most common oral therapies for dermatophyte toenail onychomycosis include terbinafine, itraconazole and fluconazole.Objectives  A cumulative meta-analysis of the randomized controlled trials (RCTs) for antimycotic agents was performed to determine whether the pooled estimate of the cure rates has remained consistent over the years. Furthermore, for each agent we compared the overall meta-analytical average of both mycological and clinical response rates of RCTs vs. open studies.Methods  We searched MEDLINE (1966 to November 2002) for relevant studies evaluating the efficacy of the oral antifungal agents terbinafine, itraconazole (pulse or continuous), fluconazole and griseofulvin for treating dermatophyte toenail onychomycosis. Studies included in this meta-analysis required a standard accepted dosage regimen, treatment duration and follow-up period. To determine the cumulative meta-analytical average, studies were sequentially pooled by adding one study at a time according to the date of publication (i.e. earliest to the most recent).Results  There were 36 studies included in the analyses. For RCTs the change in efficacy of mycological cure rates from the first trial to the overall cumulative meta-average for each drug comparator is as follows (with 95% confidence interval): terbinafine, 78 ± 6% (n = 2 studies, 79 patients) to 76 ± 3% (n = 18 studies, 993 patients) (P = 0·68); itraconazole pulse, 75 ± 10% (n = 1 study, 20 patients) to 63 ± 7% (n = 6 studies, 318 patients) (P = 0·25); itraconazole continuous, 63 ± 5% (n = 1 study, 84 patients) to 59 ± 5% (n = 7 studies, 1131 patients) (P = 0·47); fluconazole, 53 ± 6% (n = 1 study, 72 patients) to 48 ± 5% (n = 3 studies, 131 patients) (P = 0·50); and griseofulvin, 55 ± 8% (n = 2 studies, 109 patients) to 60 ± 6% (n = 3 studies, 167 patients) (P = 0·41). The cumulative meta-analytical average of mycological cure rates when comparing RCTs vs. open studies was: terbinafine, 76 ± 3% (n = 18 studies, 993 patients) vs. 83 ± 12% (n = 2 studies, 391 patients) (P = 0·0028); itraconazole pulse, 63 ± 7% (n = 6 studies, 318 patients) vs. 84 ± 9% (n = 3 studies, 194 patients) (P = 0·0001); and fluconazole, 48 ± 5% (n = 3 studies, 131 patients) vs. 79 ± 3% (n = 3 studies, 208 patients) (P = 0·0001).Conclusions  The cumulative meta-analysis of cure rates for RCTs suggests that over time, as new RCTs have been conducted, the efficacy rates have remained consistent. The efficacy rates of open studies are substantially higher compared with RCTs and may therefore overestimate cure rates.

Notes: Background We have recently observed that women with the eating disorders (EDs) anorexia nervosa and bulimia nervosa report a significantly greater (P = 0·002) dissatisfaction with the appearance of their skin than do non-clinical controls.Objectives To examine further the nature of the dissatisfaction with skin appearance in women with EDs.Methods Several psychosocial and body image parameters, including whether or not the subjects were satisfied with a wide range of attributes associated with non-diseased skin, were surveyed in women aged ≤ 30 years. Survey data from 32 women with EDs and 34 randomly selected community-based non-clinical controls were examined.Results Eighty-one per cent of the patients with EDs vs. 56% of the controls reported dissatisfaction with the appearance of their skin (P = 0·03), particularly with respect to its dryness and roughness. Other attributes that were rated more frequently were ‘bags’ and ‘darkness’ under the eyes, freckles, fine wrinkles and patchy hyperpigmentation.Conclusions There is a high prevalence of dissatisfaction with skin appearance among women aged ≤ 30 years, which is even higher among patients with EDs.

Notes: Summary  Background With the development of newer antifungal agents with activity against both yeasts and filamentous fungi, there is an increased need to develop and standardize in vitro assays that will evaluate the activity of antimycotics against filamentous fungi. In vitro analysis of antifungal activity of these agents would also allow for the comparison between different antimycotics, which in turn may clarify the reasons for lack of clinical response or serve as an effective therapy for patients with chronic infection. Objectives To determine the in vitro susceptibility of fungal organisms to ciclopirox, terbinafine, ketoconazole and itraconazole and to evaluate the in vitro activity and mode of interaction of ciclopirox in combination with either terbinafine or itraconazole. Materials and methods In the minimum inhibitory concentration (MIC) study 133 strains were evaluated, including dermatophytes (110 strains; 98 from Trichophyton spp.), Candida spp. (14 strains) and nondermatophyte moulds (nine strains). In vitro susceptibility testing was conducted in microbroth dilutions based on the National Committee for Clinical Laboratory Standards (NCCLS) M27-A proposed standard. The testing MIC ranges were 0·003–2 μg mL−1 for ciclopirox and terbinafine, and 0·06–32 μg mL−1 for itraconazole and ketoconazole. For inoculum preparation, dermatophytes were grown on Heinz oatmeal cereal agar slants. Inoculum suspensions of dermatophytes were diluted in RPMI 1640 (Sigma-Aldrich) with the desired final concentration being 2–5 × 103 c.f.u. mL−1. Once inoculated, the microdilution plates were set up according to the NCCLS M27-A method, incubated at 35 °C, and read visually following 7 days of incubation. For azole agents, the MIC was the lowest concentration showing 80% growth inhibition; for terbinafine and ciclopirox, the MIC was the lowest concentration showing 100% growth inhibition. In the synergy studies, 29 strains from nondermatophyte species were evaluated using a checkerboard microdilution method. The concentrations tested were: 0 and 0·06–32 μg mL−1 for itraconazole, and 0 and 0·003–4 μg mL−1 for both terbinafine and ciclopirox. Modes of interaction between drugs were classified as synergism, additivism, antagonism or indifference based on fractional inhibitory concentration index values (FIC index). Synergism was defined as an FIC index of ≤ 0·50, additivity as an FIC index of ≤ 1·0, and antagonism as an FIC index of ≥ 2·0. The drug combination was interpreted as indifferent if neither of the drugs had any visible effect on the presence of the other drug. Results In the MIC study, the dermatophyte MIC values (μg mL−1) (mean ± SEM) were: ciclopirox (0·04 ± 0·02), terbinafine (0·04 ± 0·23), itraconazole (2·28 ± 7·42) and ketoconazole (0·83 ± 1·99). The yeast MIC values (μg mL−1) (mean ± SEM) were: ciclopirox (0·05 ± 0·02), terbinafine (1·77 ± 0·58), itraconazole (0·18 ± 0·27) and ketoconazole (0·56 ± 0·60). The non-dermatophyte fungi MIC values (μg mL−1) (mean ± SEM) were: ciclopirox (1·04 ± 2·62), terbinafine (1·04 ± 0·95), itraconazole (17·87 ± 16·75) and ketoconazole (10·69 ± 13·09). In the synergy study, with ciclopirox in combination with terbinafine, mainly a synergistic or additive reaction was observed; there were no cases of antagonism. For ciclopirox in combination with itraconazole, there were some instances of additivism or synergism, with indifference in the majority of instances; there were no cases of antagonism. Conclusions In vitro susceptibility testing indicates that ciclopirox may have a broad antimicrobial profile including dermatophytes, yeasts and other nondermatophytes. Terbinafine is extremely potent against dermatophytes. In vitro evaluation of activity of ciclopirox and terbinafine suggests many instances of synergy or additivism; for ciclopirox and itraconazole there may be indifference, synergy or additivism.

Notes: In an open, multicentre evaluation carried out in Brazil, Canada and South Africa we have demonstrated that fluconazole 8 mg kg−1 once weekly is effective in tinea capitis caused by Trichophyton and Microsporum species. There were 61 children, aged (mean ± SE) 5·0 ± 0·3 years; weight (mean ± 5·6) 20·0 ± 0·9 kg; 41 males, 20 females; one Asian, 57 Black, one Caucasian and two Hispanic. The organisms were Trichophyton violaceum (33 patients), T. tonsurans (11) and Microsporum canis (17). The extent of tinea capitis at pretherapy was: mild (18 patients), moderate (30) and severe (13). Patients with tinea capitis due to Trichophyton species were initially treated for 8 weeks with an extra 4 weeks of fluconazole if clinically indicated. All 44 patients with tinea capitis due to Trichophyton species were completely cured (clinically and mycologically) when evaluated 8 weeks after completion of active treatment, following 8 weeks of once weekly dosing in 35 patients and 12 weeks of once weekly dosing in nine patients. In Microsporum canis tinea capitis, an extra 4 weeks was administered at week 12 in patients where it was clinically indicated at the time. Sixteen of 17 patients with M. canis tinea capitis were completely cured (clinically and mycologically) when evaluated 8 weeks following the end of treatment when given for 8, 12 and 16 weeks in 12, one and three patients, respectively. Overall, complete cure (clinical and mycological) occurred in 60 of 61 patients at follow-up 8 weeks from the end of therapy. The duration of once weekly fluconazole in the 60 patients was 8 weeks (47 patients), 12 weeks (10 patients) and 16 weeks (three patients), respectively. Clinical adverse effects consisted of a mild, reversible gastrointestinal complaint in three (4·9%) of 61 children. A laboratory abnormality with elevated liver function tests was observed in one (5·9%) of 17 patients; this was asymptomatic, and reversible. No patient discontinued therapy. The data suggest that once weekly fluconazole dosing is effective, safe and associated with high compliance when used to treat tinea capitis.

Notes: Fifty-five strains, either authentic or ex-type, of seven Malassezia species were investigated for in vitro susceptibility to various concentrations (0·03–64·0 µg/mL) of three azole drugs, ketoconazole, voriconazole and itraconazole, as well as the allylamine terbinafine, using the agar dilution method. All strains of the seven Malassezia species were susceptible to the three azole drugs at low concentrations. M. furfur, M. sympodialis, M. slooffiae, M. pachydermatis, M. globosa, M. obtusa and M. restricta were most sensitive to ketoconazole and itraconazole, with minimum inhibitory concentrations (MICs) ranging from ≤ 0·03 to 0·125 μg/mL. The recently introduced antifungal, voriconazole, was also very effective, with MIC80 values ≤ 0·03 μg/mL for 80% of strains. MICs of terbinafine against the seven Malassezia species ranged from ≤ 0·03 to 64·0 μg/mL. There were variations in susceptibility of the seven Malassezia species to ketoconazole, voriconazole, itraconazole and terbinafine. Strains of M. furfur, M. globosa and M. obtusa were more tolerant to terbinafine than the remaining Malassezia species; M. sympodialis was highly susceptible. M. furfur strains tested with terbinafine ranged from highly susceptible to relatively resistant. Correct identification of Malassezia species could facilitate selection of appropriate antifungal therapy.

Notes: At the one-stop carpal tunnel syndrome clinic, patients undergo neurophysiological studies followed by clinical assessment by the orthopaedic consultant on the same day. Patients with paraesthesia or numbness in the median nerve distribution for greater than three months duration without a history of a previous soft tissue neck injury were selected for assessment in the one-stop carpal tunnel syndrome clinic based on a proforma completed by their general practitioners. Data of patients attending the one-stop carpal tunnel syndrome clinic over a ten-month period were compared with that over the same period from a conventional hand clinic. A total of 77 patients attended the one-stop carpal tunnel syndrome clinic over a ten-month period. The mean time from referral to surgery was 23 weeks in this group compared to 44 weeks for a conventional clinic. On average, the one-stop carpal tunnel syndrome clinic reduced the time from referral to surgery by 21 weeks. The one-stop carpal tunnel syndrome clinic is convenient and cost effective for patients and hospitals.

Notes: The thrust of this paper is to develop a comprehensive software selection criterion and view information technology related issues in supply chain management. This paper furnishes implicit details of decision support systems, software solutions and factors associated with selection of IT applications for supply chain management. It entails the components of decision support systems and evolution of supply chain management softwares. A brief discussion of the functioning of various modules of the supply chain package is presented. This paper also proposes the use of percentage based weighted Tree in order to choose appropriate supply chain solution(s).