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Background: Despite decades of use, the magnitude of efficacy of narrowband ultraviolet B (NB-UVB) phototherapy for atopic dermatitis (AD) beyond industry-sponsored trials remains unclear., Aim: To evaluate the clinical efficacy of NB-UVB in AD under real-world conditions., Methods: We conducted a historical inception cohort study using automated recording of dispensed drugs to provide an objective treatment outcome in a large population catchment of 420 000 people over 15 years. We analysed clinical treatment outcomes, recorded multicentre and prospectively over 15 years, of a large AD treatment cohort (n = 844), along with the drugs dispensed to this cohort., Results: The majority (70%) of patients with AD received significantly fewer topical corticosteroids (TCS) during the 12-month window after finishing NB-UVB compared with the 12-month window before starting the treatment (median reduction from 37.5 to 19.7 g/month). The number of patients dispensed with oral corticosteroids and antihistamines also dropped significantly (from 20% to 10% and from 69% to 31%, respectively), while all AD-unrelated drugs dispensed remained unchanged. Clinically, NB-UVB treatment achieved a 'clear' or 'almost clear' status in 48.7% of patients, while 20.4% achieved 'moderate clearance'. Treatment outcomes scores were validated by a strong correlation with reduction in AD-specific drug treatment., Conclusion: Our data confirm the significant efficacy of NB-UVB for AD under conditions of routine care., (© 2021 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Despite decades of use, the actual amounts of topical corticosteroids (TCS) and emollients used in moderate-to-severe atopic dermatitis (AD) under real-world conditions are unknown. Thus, it remains unclear whether inadequate use is widespread., Objectives: To quantify the use of TCS and emollients in moderate-to-severe AD., Methods: Double-blinded drug prescribing was recorded prospectively at the point of drug dispensing within a catchment area of approximately 450 000 people over a 31-year period in a population-based cohort marked by failure of disease control in primary care (n = 844). For each patient, prescribing was recorded over a 12-month period in order to minimize fluctuations., Results: This approach resulted in a near-complete dataset, which was essentially free of reporting bias and recording bias. Atopic comorbidities matched expected frequencies. Median use of TCS was statistically significantly higher in juvenile patients (age < 16 years) compared with adult patients (49·2 vs. 38·1 g per month), in male vs. female patients (46·8 vs. 29·7 g per month) and in patients receiving concurrent asthma treatment (40·4 vs. 26·7 g per month). TCS use was strongly associated with antidepressant treatment. Emollient use was unexpectedly low with a median of 9·6 g per day (range 1·4-30·1). Results were replicated in an independent validation cohort., Conclusions: Deficient use of emollients may be a factor contributing to AD severity. Our analysis showed that the use of TCS does not exceed current guidelines. Accurate quantification of topical treatments provides a widely accessible strategy to measure the real-world impact of novel AD treatments. What's already known about this topic? Both emollient and topical corticosteroid (TCS) use have been a mainstay of atopic dermatitis (AD) treatment for over 60 years. The actual quantities used by patients under real-world conditions are unknown. What does this study add? The real-world use of emollients is fourfold lower than the amount recommended in current guidelines. Underuse of emollients may be a significant factor in disease exacerbation. The use of TCS is significantly higher in male patients and is higher in patients with AD who also have asthma. The use of TCS is strongly associated with concurrent antidepressant treatment., (© 2019 British Association of Dermatologists.)

Background: Narrowband ultraviolet B (NB-UVB) treatment for psoriasis is considered expensive. However, existing data are based on estimates and do not consider indirect cost savings., Objectives: To define the actual costs of NB-UVB incurred by the service provider, as well as treatment-associated cost savings., Methods: We performed data linkage of (i) comprehensive treatment records and (ii) prescribing data for all NB-UVB treatment episodes spanning 6 years in a population of 420 000. We minimized data fluctuation by compiling data from four independent treatment sites, and using drug prescriptions unrelated to psoriasis as a negative control., Results: National Health Service Tayside spent an average of £257 per NB-UVB treatment course (mean 257 ± 63, range 150-286, across four independent treatment sites), contrasting sharply with the estimate of £1882 used by the U.K. National Institute for Health and Care Excellence. The cost of topical treatments averaged £128 per patient in the 12 months prior to NB-UVB, accounting for 42% of the overall drug costs incurred by these patients. This was reduced by 40% to £53 per patient over the 12-month period following NB-UVB treatment, while psoriasis-unrelated drug prescription remained unchanged, suggesting disease-specific effects of NB-UVB. The data were not due to site-specific factors, as confirmed by highly similar results observed between treatment sites operated by distinct staff. Finally, we detail all staff hours directly and indirectly involved in treatment, allowing direct translation of cost into other healthcare systems., Conclusions: NB-UVB is a low-cost treatment; cost figures currently used in health technology appraisals are an overestimate based on the data presented here. Creating or extending access to NB-UVB is likely to offer additional savings by delaying or avoiding costly third-line treatments for many patients., (© 2018 British Association of Dermatologists.)

It is well documented that patients with human leucocyte antigen (HLA)-Cw6+ (type 1) psoriasis have increased severity and reduced age of onset of psoriasis. However, not much is known about any differential response of this genetic subgroup to various treatments. We set out to determine if there was any genetic association of the HLA-Cw6 allele with the first-line systemic treatment commonly used in psoriasis, methotrexate. A cohort of patients from Tayside in Scotland was recruited through a novel generic consenting process (GoShare); they were extensively phenotyped and analysed for an association of their HLA-Cw6 genotype status with treatment outcomes. HLA-Cw6+ patients showed notably improved response to methotrexate (P = 0.05), and further analysis demonstrated an even greater response in a subcohort of the HLA-Cw6+ patients, who did not have concomitant psoriatic arthritis (P = 0.01). HLA-Cw6+ patients also exhibited fewer treatment-limiting adverse events. In addition to these findings, the methodology and primary clinical outcome phenotype, which we validate here, will greatly facilitate replication of the present results in independent cohorts., (© 2017 British Association of Dermatologists.)

Background: Phenotypically diverse autoimmune conditions share common genetic susceptibility loci and underlying molecular pathways., Objectives: By systematically searching for single nucleotide polymorphisms (SNPs) associated with another autoimmune disease, rheumatoid arthritis (RA), we aimed to elucidate novel genetic markers of psoriasis., Methods: We investigated 18 SNPs, previously confirmed as being associated with RA, in a U.K. cohort of 623 patients with early-onset psoriasis (presenting before age 40 years), comparing them with 2662 control subjects., Results: Our findings confirm the association of early-onset psoriasis with REL (rs13031237, P=0·0027). The minor allele of REL had opposing effects upon susceptibility to disease in patients with psoriasis and RA., Conclusion: Similar exploration of additional autoimmune loci and fine mapping of such regions may provide further insight into the genetics and molecular pathophysiology of psoriasis., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Plasmacytoid dendritic cells (pDCs) fulfil multiple roles in immunity, and can secrete large amounts of interferon (IFN)-α. However, the available evidence suggests that they may actually counteract efficient antitumour immunity. Thus in melanoma, pDCs are abundant, but they are anergic and deficient in IFN-α secretion. pDC anergy is thought to be caused by immunosuppressive factors secreted by melanoma cells. One factor strongly expressed by melanoma is Wnt5a, which is implicated in cancer tissue invasion. In this paper, we show that Wnt5a is able to block the upregulation of the activation markers CD80 and CD86 on naive human pDCs stimulated by CpG oligodeoxynucleotide, and CpG-triggered secretion of IFN-α by pDCs. Our results suggest that Wnt5a may not only initiate cancer invasion, but could also regulate activation of pDC. These data provide a clear rationale to investigate a role for Wnt5a in immune regulation., (© The Author(s). CED © 2012 British Association of Dermatologists.)

Fumaric acid esters (FAE) have been used in the treatment of psoriasis for many years. In general, they are regarded as relatively safe compared with other antipsoriatic systemic treatments, with the most notable adverse effects being gastrointestinal upset, lymphopenia and transient flushing. Renal toxicity has only rarely been reported, and was not found in two independent prospective trials nor in a large retrospective evaluation of almost 1000 patients treated for a median of 44 months. We report three patients developing reversible proteinuria during FAE treatment. One of these displayed the same pattern upon repeated drug administration, thereby clearly indicating FAE treatment to be the causal trigger. The presented cases highlight proteinuria as a clinical concern in FAE treatment. Furthermore, as the novel FAE agent dimethylfumaric (DMF) ester (contained in BG00012/Panaclar) has previously been shown to be effective in psoriasis in a phase III trial and not shown renal toxicity in a large trial for multiple sclerosis, the current report suggests that market introduction of DMF for psoriasis should be pursued., (© The Author(s). CED © 2011 British Association of Dermatologists.)

Background: The production of reactive oxygen species (ROS) by fibroblasts has been suggested to contribute to scleroderma pathogenesis. Infrared-mediated hyperthermia has recently been shown to be of benefit in scleroderma., Aim: As the contribution of neutrophils and monocytes to ROS formation in scleroderma is unknown, we studied respiratory burst in these cell types. We also aimed to test the hypothesis that near-infrared (IRA) treatment may effect burst activity., Methods: We determined respiratory burst in patients with scleroderma (n = 22) and age- and sex-matched controls (n = 20) at baseline, and after high-level stimulation by phorbolmyristyl acetate (PMA) and low-level stimulation by non-opsonized zymosan. Respiratory burst was also assessed before and after a series of infrared-mediated hyperthermia treatments., Results: Unexpectedly, we observed no increase but instead a slight but statistically significant reduction in baseline and zymosan-stimulated respiratory burst in scleroderma neutrophils (P < 0.001) and monocytes (P < 0.005). This decrease in burst activity was nonspecific, as it was also observed in patients with another active inflammatory disease, psoriasis. IRA treatment induced a cell-type-specific normalization of respiratory burst only in neutrophils, but not in monocytes. Intriguingly, neutrophil-specific normalization of ROS formation persisted for 6 weeks after the end of IRA treatment, in concordance with the previously reported clinical responses to this therapy., Conclusion: Neutrophils and monocytes do not exhibit cell-autonomous overproduction of ROS in scleroderma, thereby implicating fibroblasts as main source for clinically relevant ROS accumulation. Furthermore, repeated mild infrared-mediated hyperthermia exerts a lasting cell-type-specific effect on neutrophils.

Background: Evaluation of treatments for Raynaud's phenomenon (RP) requires objective response parameters in addition to clinical activity scores. Thermographic monitoring of fingertip re-warming after cold challenge has been widely used but usually requires sophisticated equipment. We have previously shown that fingertip re-warming after cold challenge follows a first-order transient response curve that can be described by a single variable, designated tau., Objectives: Here, we describe a novel device termed a duosensor, which records the tau value upon cold challenge in an automated manner., Methods: We determined tau values in healthy probands, patients with primary or secondary RP associated with autoimmune disease and patients with scleroderma-associated RP following cold challenge, to determine assay variability, sensitivity and specificity., Results: Duosensor-based thermography exhibited low intraindividual variability in healthy probands. As expected, tau values in RP patients were significantly increased compared with controls (8.08 +/- 3.65 min vs. 3.23 +/- 1.65 min). The duosensor-determined tau value yielded a specificity of 94.6% and predictive value of 95.3% for the presence of RP in a retrospective analysis of 139 patients. Furthermore, in a cohort of scleroderma patients with RP, patient self-assessment of RP severity correlated with tau values., Conclusions: Taken together, the present data suggest that tau value determination provides a suitable outcome measure for clinical studies of novel RP treatments. As the duosensor is a simple stand-alone device requiring no supporting equipment and minimal personnel attention, it should allow RP activity monitoring even in clinical settings with minimal technical infrastructure.

The small-scale distribution pattern of macroalgae in the river Ilm, in Germany was monitored. These patterns were then related to abiotic factors and tested to discover whether the distribution of the common macroalgae, Cladophora glomerata (L.) Kütz. and Vaucheria sp., was linked to differences in their photosynthetic plasticity. Cladophora glomerata revealed higher maximum photosynthetic electron transport rates after acclimation to high light (HL) compared with low light (LL) acclimated samples. By contrast, Vaucheria sp. did not acclimate to different growth light conditions. The photosynthetic performance of both algae also varied according to diurnal conditions. High light caused a reversible decrease of the dark-adapted quantum yield (F(v)/F(m)) in C. glomerata and a concomitant reversible decrease of the light-adapted quantum yield (DeltaF/F'(m)). In Vaucheria sp., F(v)/F(m) remained mostly unchanged over the day, whereas DeltaF/F'(m) decreased during the morning at low light. Photosynthetic pigments confirmed acclimational differences between the species. HL C. glomerata showed increased chlorophyll a:chlorophyll b ratios, and higher amounts of xanthophyll-cycle pigments compared with LL samples, whereas Vaucheria sp. did not reveal differences between the light treatments. While preferences for substrate size, water velocity, and depth are similar for C. glomerata and Vaucheria sp., the physiological responses to light conditions are different. It is concluded that light conditions significantly affect the small-scale spatial distribution of macroalgae and that fitness is enhanced in species with a higher plasticity in photosynthetic acclimation in unstable environments.

This article introduces a new approach for restoring endodontically treated posterior teeth. Significantly reduced natural tooth structure often remains not only because of previous restorative measures but also because of endodontic procedures. Cast restorations for these teeth are almost universally recommended. The exception to this is the rare instance in which only conservative endodontic access openings exist in teeth presenting with no former existing restorations. Typically, multiple clinical appointments are required to complete the final cast restoration. This article presents Computer-Aided Design and Computer-Assisted Manufacturing/Computer-Aided Design and Computer-Integrated Manufacturing applications for restorative dentistry that provide the necessary care in an expeditious manner.