Recommendations from the Spanish Academy of Dermatology and Venereology Psoriasis Working Group on the Management of Patients with Cancer and Psoriasis. / Recomendaciones del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología sobre el manejo de la psoriasis en pacientes oncológicos.

Several studies suggest that patients with psoriasis have a higher incidence of neoplasms, especially of the skin, which could be associated with the use of therapies to treat psoriasis. Furthermore, the evidence available on the safety profile of some treatments in this context, and the management of these patients is scarce, which is why clinical practice guidelines with recommendations on the management of psoriasis in cancer patients are ambiguous. This study provides recommendations on the management and use of the therapies currently available for these patients. They are the result of a Delphi consensus reached by 45 dermatologists of the Spanish Academy of Dermatology and Venereology Psoriasis Working Group, whose goal is to help specialists in the field in their decision-making processes.

Selection of Quality Indicators for the Certification of Psoriasis Units: The CUDERMA Project Delphi Consensus Study. / Proyecto CUDERMA: Consenso Delphi de los indicadores de calidad para la certificación de las unidades de dermatología de atención en psoriasis.

Defining quality indicators is a key strategy for ensuring the quality and standardization of health care. The CUDERMA project, an initiative of the Spanish Academy of Dermatology and Venerology (AEDV), was undertaken to define quality indicators for the certification of specialized units in dermatology; the first 2 areas selected were psoriasis and dermato-oncology. The aim of this study was to reach a consensus on what should be assessed by the indicators used to certify psoriasis units. The structured process used to do this comprised a literature review to identify potential indicators, the selection of an initial set of indicators to be evaluated by a multidisciplinary group of experts and, finally, a Delphi consensus study. A panel of 39 dermatologists evaluated the selected indicators and classified them as either "essential" or "of excellence". Consensus was finally reached on 67 indicators, which will be standardized and used to develop the certification standard for psoriasis units.

Expert consensus on the persistence of biological treatments in moderate-to-severe psoriasis.

BACKGROUND: Treatment persistence is becoming a useful measure to evaluate long-term effectiveness and safety of biological therapies in real-world settings. OBJECTIVE: The main objective of this study was to explore the scientific opinion of a panel of dermatologists and hospital pharmacists to reach a consensus about the impact, causes, and best strategies and interventions that might be associated with improved drug persistence in patients with psoriasis in Spain. METHODS: This research was conducted using a modified Delphi method organized in two rounds and involving a panel of 90 dermatologists and 34 hospital pharmacists. A questionnaire of 70 items was developed. The items proposed to reach a consensus included topics such as definitions and measures in the treatment of psoriasis, analysis of treatment persistence, factors that may influence treatment persistence, impact of treatment persistence and economic cost of treatment. RESULTS: Dermatologists reached a consensus on 77.1% of the items proposed, and hospital pharmacists reached a consensus on 71.4%. Both groups agreed that it is important to use standardized measures in the evaluation of treatment maintenance over time. Dermatologists agreed that treatment survival, persistence and retention are synonymous, but hospital pharmacists considered only treatment persistence as a valid term. In addition, panelists agreed that drug persistence is an indicator of success in the treatment of psoriasis that may be influenced by a drug's effectiveness and safety profile, as well as by patient satisfaction. They agreed that the different causes of treatment discontinuation should be considered in Kaplan-Meier analysis of treatment persistence. Moreover, treatment persistence was agreed to decrease the cost of therapy. CONCLUSION: This Delphi consensus highlights the different perspectives of dermatologists and hospital pharmacists regarding the interpretation of treatment persistence, and the challenge of harmonizing the results obtained.

Initial results of ixekizumab efficacy and safety in real-world plaque psoriasis patients: a multicentre retrospective study.

BACKGROUND: Ixekizumab (anti-IL17A) is effective as treatment for moderate-to-severe plaque psoriasis, but real-life data on effectiveness and safety are currently very limited. OBJECTIVE: To evaluate the efficacy and safety of ixekizumab in a cohort of real-life plaque psoriasis patients. METHODS: Retrospective chart review of 100 patients with moderate-to-severe plaque psoriasis treated with ixekizumab at seven Spanish dermatological centres. RESULTS: According to the as observed analysis, the percentage of patients achieving a 75% and 90% of reduction from the baseline score of Psoriasis Area and Severity Index (PASI) was 87.5%-50.0% at week 12-16; 88.3%-58.4% at week 24 and 82.9%-58.5% at week 52, respectively. The mean ± standard deviation (SD) score of PASI at baseline was 12.9 ± 9.2, and it declined rapidly after ixekizumab administration to 1.9 ± 4.0 (P < 0.001) at week 12-16 and was maintained at 1.7 ± 4.1 and 1.8 ± 2.9 at week 24 and 52, respectively. Ixekizumab response was not affected by clinical variables like body mass index, disease duration or the presence of psoriatic arthritis. However, the bio-naive group showed significantly higher PASI 75 response rate at week 12-16 compared to patients previously exposed to biologic agents (P = 0.037). Twenty-six (26%) patients experienced adverse events (AEs) during the follow-up period, being most of them of mild-to-moderate intensity. The most common AE was local reaction at the site of injection (14/26; 53.8%). At the end of the observational period, 15 (15%) patients discontinued ixekizumab treatment due to limited clinical improvement (n = 11), adverse events (n = 3) or lost to follow-up (n = 1) within a mean ± SD time of 6.0 ± 3.9 months. CONCLUSION: The present study illustrates the initial experience with ixekizumab in real-world clinical practice confirming its usefulness and safety in the management of plaque psoriasis patients.

Moderate Psoriasis: A Proposed Definition. / Psoriasis moderada. Propuesta de definición.

INTRODUCTION: The Psoriasis Area Severity Index (PASI) is the most widely used scale for assessing the severity of psoriasis and for therapeutic decision making. On the basis of the PASI score, patients have been stratified into 2 groups: mild disease and moderate-to-severe disease. OBJECTIVE: To draft a proposal for the definition and characterization of moderate psoriasis based on PASI and Dermatology Life Quality Index (DLQI) scores. MATERIAL AND METHODS: A group of 6 dermatologists with experience in the treatment of psoriasis undertook a critical review of the literature and a discussion of cases to draft a proposal. RESULTS: In order of priority, PASI, DLQI, and body surface area (BSA) are the parameters to be used in daily practice to classify psoriasis as mild, moderate, or severe. Severity should be assessed on the basis of a combined evaluation and interpretation of the PASI and DLQI. And 3, PASI and DLQI should carry equal weight in the determination of disease severity. On this basis, psoriasis severity was defined using the following criteria: mild, PASI<7 and DLQI<7; moderate, PASI=7-15 and DLQI=5-15 (classified as severe when difficult-to-treat sites are affected or when there is a significant psychosocial impact); severe, PASI >15, independently of the DLQI score. CONCLUSIONS: A more precise classification of psoriasis according to disease severity will improve the risk-benefit assessment essential to therapeutic decision making in these patients.

Use of biological treatments in patients with hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic skin disease which causes a great impact in the quality of life. Multiple therapeutic options have been proposed, and recently the potential use of biological drugs in severe cases has been postulated. MATERIAL AND METHODS: A retrospective study from seven tertiary Spanish centers reviewing the charts of patients with HS treated with biological drugs was performed. Retrieved information included epidemiological data, clinical features, pain intensity, Hurley stage, laboratory data and therapeutic outcomes. RESULTS: Nineteen patients were included in the study; 10 men (52.6%) and 9 women. Eight patients (42%) showed a Hurley severity stage II and 11 a stage III (57.8%). Adalimumab was prescribed as the first biological treatment in nine out of 19 cases (47.3%), whereas infliximab was prescribed in seven cases (36.8%), ustekinumab in two cases (10.5%) and etanercept in one (5.2%). A complete response was observed in three patients (two cases with infliximab and one case with ustekinumab), a partial improvement in 10 patients and in six patients no clinical improvement was noted. One patient referred worsening of the skin symptoms. In 6 cases, a second biological treatment was prescribed. In three of such cases, a partial improvement was noted, whereas in three cases no clinical improvement was observed. In two cases a switch to a third biological drug was indicated, with a partial improvement in one case. DISCUSSION AND CONCLUSIONS: Biological drugs could be a potential and effective therapeutic option for patients with severe HS. Complete and persistent clinical responses are rarely obtained (15%) and partial responses are achieved in approximately 50% of patients. No specific markers for a therapeutic response have been identified. No definitive conclusions regarding the most effective biological drug for HS could be drawn. Higher dosage schedules seem to be associated with higher response rates. The lack of response of one particular drug does not preclude a potential efficacy to another biological treatment.

Terahertz Detection by Asymmetric Dual Grating Gate Bilayer Graphene FETs with Integrated Bowtie Antenna.

An asymmetric dual-grating gate bilayer graphene-based field effect transistor (ADGG-GFET) with an integrated bowtie antenna was fabricated and its response as a Terahertz (THz) detector was experimentally investigated. The device was cooled down to 4.5 K, and excited at different frequencies (0.15, 0.3 and 0.6 THz) using a THz solid-state source. The integration of the bowtie antenna allowed to obtain a substantial increase in the photocurrent response (up to 8 nA) of the device at the three studied frequencies as compared to similar transistors lacking the integrated antenna (1 nA). The photocurrent increase was observed for all the studied values of the bias voltage applied to both the top and back gates. Besides the action of the antenna that helps the coupling of THz radiation to the transistor channel, the observed enhancement by nearly one order of magnitude of the photoresponse is also related to the modulation of the hole and electron concentration profiles inside the transistor channel by the bias voltages imposed to the top and back gates. The creation of local n and p regions leads to the formation of homojuctions (np, pn or pp+) along the channel that strongly affects the overall photoresponse of the detector. Additionally, the bias of both back and top gates could induce an opening of the gap of the bilayer graphene channel that would also contribute to the photocurrent.

Impact of device resistances in the performance of graphene-based terahertz photodetectors.

In recent years, graphene field-effect-transistors (GFETs) have demonstrated an outstanding potential for terahertz (THz) photodetection due to their fast response and high-sensitivity. Such features are essential to enable emerging THz applications, including 6G wireless communications, quantum information, bioimaging and security. However, the overall performance of these photodetectors may be utterly compromised by the impact of internal resistances presented in the device, so-called access or parasitic resistances. In this work, we provide a detailed study of the influence of internal device resistances in the photoresponse of high-mobility dual-gate GFET detectors. Such dual-gate architectures allow us to fine tune (decrease) the internal resistance of the device by an order of magnitude and consequently demonstrate an improved responsivity and noise-equivalent-power values of the photodetector, respectively. Our results can be well understood by a series resistance model, as shown by the excellent agreement found between the experimental data and theoretical calculations. These findings are therefore relevant to understand and improve the overall performance of existing high-mobility graphene photodetectors.

Guidelines for the use of acitretin in psoriasis. Psoriasis Group of the Spanish Academy of Dermatology and Venereology.

Phototherapy, classic systemic treatments (methotrexate, acitretin, and ciclosporin), and biologic agents (etanercept, infliximab, adalimumab, and ustekinumab) constitute a broad therapeutic arsenal that increases the likelihood of achieving control of severe and extensive disease in patients with psoriasis. Acitretin continues to be a very valuable tool in both monotherapy, in which it is combined with other systemic treatments (classic or biologic), and in sequential therapy. Thanks to its lack of a direct immunosuppressive effect and its ability to achieve a long-term response, acitretin has an important role in the treatment of psoriasis, although this has not always been acknowledged in relevant treatment guidelines. We present consensus guidelines for the use of acitretin in psoriasis drawn up by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology. These guidelines provide a detailed account of acitretin, including pharmacological properties, indications and contraindications, adverse effects, and factors that should be taken into account to enhance the safe use of this drug. They also propose treatment strategies for use in routine clinical practice. The overall aim of these guidelines is to define the criteria for the use and management of acetretin in psoriasis.

Spanish evidence-based guidelines on the treatment of psoriasis with biologic agents, 2013. Part 1: on efficacy and choice of treatment. Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology.

Biologic therapy is a well-established strategy for managing moderate and severe psoriasis. Nevertheless, the high cost of such therapy, the relatively short span of clinical experience with biologics, and the abundance of literature now available on these agents have made evidence-based and consensus-based clinical guidelines necessary. The ideal goal of psoriasis treatment is to achieve complete or nearly complete clearing of lesions and to maintain it over time. Failing that ideal, the goal would be to reduce involvement to localized lesions that can be controlled with topical therapy. Although current evidence allows us to directly or indirectly compare the efficacy or risk of primary or secondary failure of available biologics based on objective outcomes, clinical trial findings cannot be directly translated to routine practice. As a result, the prescribing physician must tailor the treatment regimen to the individual patient. This update of the clinical practice guidelines issued by the Spanish Academy of Dermatology and Venereology (AEDV) on biologic therapy for psoriasis incorporates information from the most recent publications on this topic.

[Guidelines on the use of methotrexate in psoriasis]. / Metotrexato: guía de uso en psoriasis.

Psoriasis, a chronic multifactorial inflammatory disease that develops in genetically predisposed individuals, affects approximately 1.5% of the Spanish population. This disease has a negative impact on patients' quality of life, and long-term therapy is often required to control the symptoms. In addition to the classical systemic treatments (methotrexate, acitretin, cyclosporine, and ultraviolet light), the group of drugs known as biologics (etanercept, infliximab, adalimumab, and ustekinumab) provides the dermatologist with an expanded therapeutic armamentarium, thereby improving the likelihood of controlling psoriasis in patients with severe and/or extensive disease. Methotrexate, a classic antipsoriatic drug, is still very useful either as single-drug therapy or in combination with other systemic drugs, particularly as a rescue therapy or combined with biologics. This article aims to establish the role of methotrexate in the treatment of psoriasis. We considered it of interest to develop guidelines for using methotrexate in the management of psoriasis with a view to ensuring the safe and proper use of this drug in the management of psoriasis. This document was developed by consensus among members of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology.

Guidelines on the Use of Methotrexate in Psoriasis. / Metotrexato: guía de uso en psoriasis.

Psoriasis, a chronic multifactorial inflammatory disease that develops in genetically predisposed individuals, affects approximately 1.5% of the Spanish population. This disease has a negative impact on patients' quality of life, and long-term therapy is often required to control the symptoms. In addition to the classical systemic treatments (methotrexate, acitretin, cyclosporine, and ultraviolet light), the group of drugs known as biologics (etanercept, infliximab, adalimumab, and ustekinumab) provides the dermatologist with an expanded therapeutic armamentarium, thereby improving the likelihood of controlling psoriasis in patients with severe and/or extensive disease. Methotrexate, a classic antipsoriatic drug, is still very useful either as single-drug therapy or in combination with other systemic drugs, particularly as a rescue therapy or combined with biologics. This article aims to establish the role of methotrexate in the treatment of psoriasis. We considered it of interest to develop guidelines for using methotrexate in the management of psoriasis with a view to ensuring the safe and proper use of this drug in the management of psoriasis. This document was developed by consensus among members of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology.

Quantum nanoconstrictions fabricated by cryo-etching in encapsulated graphene.

We report on a novel implementation of the cryo-etching method, which enabled us to fabricate low-roughness hBN-encapsulated graphene nanoconstrictions with unprecedented control of the structure edges; the typical edge roughness is on the order of a few nanometers. We characterized the system by atomic force microscopy and used the measured parameters of the edge geometry in numerical simulations of the system conductance, which agree quantitatively with our low temperature transport measurements. The quality of our devices is confirmed by the observation of well defined quantized 2e2/h conductance steps at zero magnetic field. To the best of our knowledge, such an observation reports the clearest conductance quantization in physically etched graphene nanoconstrictions. The fabrication of such high quality systems and the scalability of the cryo-etching method opens a novel promising possibility of producing more complex truly-ballistic devices based on graphene.

Perception of psoriasis treatment in the outpatient setting: survey of patients and their prescribing physicians.

BACKGROUND: Patients' perception of disease management can influence compliance to treatment and thus affect outcome. OBJECTIVE: To survey patients and physicians on their perceptions of biologic therapy for treating psoriasis in an outpatient setting. METHODS: The subjective impact of intravenous treatment of severe psoriasis on patients and physicians in the outpatient setting was determined via two surveys. RESULTS: Between September and November 2014, 24 dermatologists and 90 patients were surveyed. Treatment with biologic agents in the outpatient setting was associated with a high level of patient satisfaction: 93.3% of patients considered their psoriasis well controlled and 46.1% reported complete control. Patients highly valued the feeling of greater disease control (72.2%), regular follow-up (66.7%) and rapid improvement of psoriasis (58.9%) when attending an outpatient setting. Other positive aspects of outpatient treatment were control of other health issues and perceived improvements in quality of life (QoL). Outpatient attendance was high; with 90% of patients keeping scheduled appointments and 79.2% of physicians acknowledged that they were able to monitor their patients' condition more closely. CONCLUSION: Administration of treatment in an outpatient setting may provide a feeling of improved QoL and disease control.

Liposomes as alternative vehicles for sun filter formulations.

The aim of our study was to determine the influence of several types of liposomes with a different lipid composition on the percutaneous absorption of one conventional sun filter with a lipophilic character (ethyl hexyl methoxycinnamate) using both in vitro and in vivo methodologies. Three different liposomes were prepared with unsaturated and saturated phosphatidylcholine (PC, HPC), and with a wool lipid mixture (IWL) with a composition similar to that of the stratum corneum lipids. Results showed that the liquid crystalline state associated with PC liposomes plays a key role in enhancing skin penetration. when liposomes with a composition and structural organization similar to that of the stratum corneum lipids (HPC and IWL) are used, the skin penetration is retarded, suggesting a certain reinforcement of the stratum corneum barrier. These two types of liposomes could be regarded as alternatives to conventional oil/water emulsions in the formulations of lipidic sun filters. Finally, an acceptable correlation was obtained using both in vitro and in vivo methodologies to evaluate the corresponding skin absorption profile.

[Clinical and epidemiological study of disease caused by Mycobacterium kansasii in the metropolitan area of Bilbao, Spain]. / Estudio clinicoepidemiológico de la enfermedad por Mycobacterium kansasii en el área urbana de Bilbao.

OBJECTIVE: Epidemiological description of individuals from whom Mycobacterium kansasii isolates were obtained in respiratory samples, and analysis of the isolates using molecular biological techniques. MATERIAL AND METHODS: A descriptive retrospective/ prospective study was carried out from January 1994 to April 2002 in Basurto Hospital and Santa Marina Hospital and from January 2000 to April 2002 in Cruces Hospital, Galdakao Hospital, and San Eloy Hospital. Diagnosis of the disease was performed according to American Thoracic Society criteria; other definitions were also applied to allow inclusion of all cases. Disease caused by M. kansasii in patients who were not infected with the human immunodeficiency virus (HIV) was compared with disease caused by Mycobacterium tuberculosis in a control group. Polymerase chain reaction was applied with analysis of restriction fragment length polymorphisms to differentiate between species of mycobacteria and classify them into genotypes. Amplified fragment length polymorphisms were used to recognize clones within each genotype. RESULTS: The patient charts of 334 patients in which an isolate of M. kansasii had been recorded were reviewed. We considered 220 patients to be suffering from disease caused by M. kansasii (American Thoracic Society criteria along with probable disease according to established definitions). The disease was more frequent in male patients (n=185; 84.1%) and in individuals who were not HIV positive (n=184; 83.6%). The highest incidence of disease in the Bizkaia region was found in Margen Izquierda-Encartaciones, where the rate was 8.05 per 100 000 inhabitants. In the Bilbao area, the highest rate was found in the districts lying on the outskirts. The underlying diseases were tuberculosis (20.5%), chronic obstructive pulmonary disease (25.9%), pulmonary neoplasia (7.7%), silicosis (0.9%), chronic liver disease (11.4%), and duodenal ulcer (8.6%). The most frequent constitutional symptoms were fever (39.1%), loss of appetite (23.2%), and weight loss (33.3%). Among the respiratory symptoms, the most outstanding were cough (70.9%) and expectoration (62.3%). The most frequent radiographic patterns were cavitation and pulmonary infiltration. The most common treatment regimen was rifampicin, isoniazid, and ethambutol (43.4%), and the average duration was 12 months in patients who were HIV negative. Analysis of antibiotic sensitivity, performed on 56 strains, revealed that 100% were resistant to isoniazid, while none displayed rifampicin resistance. Thirty-four cases of disease caused by M. kansasii were compared with 68 cases of tuberculosis, all of them without HIV infection. The comparison revealed a predominance of smokers, respiratory symptoms, and cavitation in patients with disease caused by M. kansasii. The majority of the isolates (98.5%) corresponded to genotype I. A total of 8 clones were obtained; the clones designated 1 and 3 were more common in HIV-positive and HIV-negative individuals respectively. CONCLUSIONS: In recent years, there has been an increase in the number of patients with disease caused by M. kansasii in the province of Bizkaia. The disease is more frequent in male patients, individuals who are HIV negative, and in urban areas. In addition, more respiratory symptoms and a higher incidence of cavitation were found in patients with disease caused by M. kansasii than in those with tuberculosis. Genotype I is the most common isolate, and clones 1 and 3 affect 80% of patients suffering from the disease.