Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema.

We recently reported two common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. We show here that these common European mutations are ancestral variants carried on conserved haplotypes. To facilitate comprehensive analysis of other populations, we report a strategy for full sequencing of this large, highly repetitive gene, and we describe 15 variants, including seven that are prevalent. All the variants are either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis. In an Irish case-control study, the five most common European mutations showed a strong association with moderate-to-severe childhood eczema (chi2 test: P = 2.12 x 10(-51); Fisher's exact test: heterozygote odds ratio (OR) = 7.44 (95% confidence interval (c.i.) = 4.9-11.3), and homozygote OR = 151 (95% c.i. = 20-1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles.

A multicenter, randomized, dose-finding study of mechanochemical ablation using ClariVein and liquid polidocanol for great saphenous vein incompetence.

BACKGROUND: The purpose of the present study was to identify the ideal polidocanol (POL) concentration for mechanochemical ablation (MOCA) of the great saphenous vein (GSV) using the ClariVein system (Merit Medical, South Jordan, Utah). METHODS: We performed a multicenter, randomized, controlled, single-blind trial with a follow-up period of 6 months. Patients with symptomatic primary truncal GSV incompetence were randomized to MOCA + 2% POL liquid (2% group) or MOCA + 3% POL liquid (3% group). The primary outcome was technical success (TS), defined as an open part of the treated vein segment of ≤10 cm in length. The secondary outcomes were alternative TS, defined as ≥85% occlusion of the treated vein segment, postoperative pain, venous clinical severity scores, Aberdeen varicose vein questionnaire scores, and short-form 36-item health survey questionnaire scores, and complications. RESULTS: From 2012 to 2018, 364 patients (375 limbs) were included, of which, 189 limbs were randomly allocated to the 2% group and 186 to the 3% group. The TS rate at 6 months was 69.8% in the 2% group vs 78.0% in the 3% group (P = .027). A higher overall TS rate was seen in GSVs of ≤5.9 mm compared with GSVs >5.9 mm (84.3% vs 59.5%, respectively; P < .001). The alternative TS rate at 6 months was 61.4% in the 2% group and 67.7% in the 3% group (P = .028). The venous clinical severity scores, Aberdeen varicose vein questionnaire scores, and most short-form 36-item health survey questionnaire domains had improved in both groups (P < .002). Postprocedural pain was low. Two pulmonary embolisms and two deep vein thromboses were seen. Superficial venous thrombosis had occurred more often in the 3% group (18 vs 8 in the 2% group; P = .033). CONCLUSIONS: The results from the present study showed a higher success rate for MOCA with 3% POL liquid than for MOCA with 2% POL liquid at 6 months of follow-up. However, the difference in quality of life was not significant. Long-term follow-up studies are required to investigate whether these results will be sustained in the future.

Use of e-learning in clinical clerkships: effects on acquisition of dermatological knowledge and learning processes.

OBJECTIVES: To obtain a deeper understanding of how the e-learning program, Education in Dermatology (ED), affects the acquisition of dermatological knowledge and the underlying learning processes of medical students in their clinical phase. METHODS: The study used a mixed method design with a convergent parallel collection of data. Medical students (n=62) from Maastricht University (The Netherlands) were randomized to either a conventional teaching group (control group n=30) or conventional teaching plus the e-learning program (application on smartphone) group (e-learning group n=32). Pre- and post-intervention knowledge test results were analysed using an independent t-test. Individual semi-structured interviews (n=9) were conducted and verbatim-transcribed recordings were analysed using King's template analysis. RESULTS: The e-learning program positively influenced students' level of knowledge and their process of learning. A significant difference was found in the post-test scores for the control group (M=51.4, SD=6.43) and the e-learning group (M=73.09, SD=5.12); t(60)=-14.75, p<0.000). Interview data showed that the e-learning program stimulated students' learning as the application promoted the identification and recognition of skin disorders, the use of references, creation of documents and sharing information with colleagues. CONCLUSIONS: This study demonstrated that use of the e-learning program led to a significant improvement in basic dermatological knowledge. The underlying learning processes indicated that e-learning programs in dermatology filled a vital gap in the understanding of clinical reasoning in dermatology. These results might be useful when developing (clinical) teaching formats with a special focus on visual disciplines.

Timing and risk factors for clinical fractures among postmenopausal women: a 5-year prospective study.

BACKGROUND: Many risk factors for fractures have been documented, including low bone-mineral density (BMD) and a history of fractures. However, little is known about the short-term absolute risk (AR) of fractures and the timing of clinical fractures. Therefore, we assessed the risk and timing of incident clinical fractures, expressed as 5-year AR, in postmenopausal women. METHODS: In total, 10 general practice centres participated in this population-based prospective study. Five years after a baseline assessment, which included clinical risk factor evaluation and BMD measurement, 759 postmenopausal women aged between 50 and 80 years, were re-examined, including undergoing an evaluation of clinical fractures after menopause. Risk factors for incident fractures at baseline that were significant in univariate analyses were included in a multivariate Cox survival regression analysis. The significant determinants were used to construct algorithms. RESULTS: In the total group, 12.5% (95% confidence interval (CI) 10.1-14.9) of the women experienced a new clinical fracture. A previous clinical fracture after menopause and a low BMD (T-score <-1.0) were retained as significant predictors with significant interaction. Women with a recent previous fracture (during the past 5 years) had an AR of 50.1% (95% CI 42.0-58.1) versus 21.2% (95% CI 20.7-21.6) if the previous fracture had occurred earlier. In women without a fracture history, the AR was 13.8% (95% CI 10.9-16.6) if BMD was low and 7.0% (95% CI 5.5-8.5) if BMD was normal. CONCLUSION: In postmenopausal women, clinical fractures cluster in time. One in two women with a recent clinical fracture had a new clinical fracture within 5 years, regardless of BMD. The 5-year AR for a first clinical fracture was much lower and depended on BMD.

Onycholysis associated with subungual manifestation of barber's hair sinus.

A female hairdresser presented with hair fragments embedded under her fingernails in association with yellow-brownish discoloration and distal detachment of the nails. Based on these findings, we made the diagnosis of subungual barber's hair sinus with onycholysis. To our knowledge, this unique clinical picture has not been reported previously. A detailed medical history revealed several risk factors that might have contributed to the disease. Here, we briefly review what is known about barber's hair sinus, an occupational disease that is usually encountered in male hairdressers and only rarely manifests in women.

Risk factors for clinical fractures among postmenopausal women: a 10-year prospective study.

OBJECTIVE: Only scarce data are available on the long-term absolute risk (AR) of all clinical fractures, taking into account the time when they occurred. Therefore, we assessed during a 10-year follow-up the risk factors associated with the occurrence of any first or second clinical fracture. STUDY DESIGN: This was a population-based study in 10 general practice centres. The sample comprised 2372 postmenopausal women, aged between 50 and 80 years at baseline, who completed a questionnaire about the incidence of radiographically confirmed fractures and fracture risks, analysed by multiple Cox regression. MAIN OUTCOME MEASURE: AR for any clinical fracture. RESULTS: During the 10-year follow-up, 380 women (16%) had a fracture. A first fracture occurred in 267 women (11%). Osteoporosis at the lumbar spine (T-score <-2.5; hazard ratio (HR) 1.8, 95% confidence interval (CI) 1.4-2.3) and age over 60 years (HR1.4, 95% CI 1.1-1.8) were the only risk factors retained in the Cox analysis. The AR in the lowest-risk group was 10%, and it was 23% in the highest-risk group. A second fracture occurred in 113 women during follow-up (5%). The time when a fracture occurred was the only risk factor retained in the Cox analysis. The AR for a second fracture was 41% in the five years after any first fracture before baseline and 25% if the first fracture had occurred earlier (HR 1.8, 95% CI 1.3-2.7). CONCLUSION: In postmenopausal women, over a 10-year follow-up, the AR of a second clinical fracture is highest in the five years after any first clinical fracture. The AR for a first clinical fracture is lower and depends on osteoporosis and age.