[Translated article] Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study. / Condicionantes de acceso a nuevos medicamentos dermatológicos en España: resultados del proyecto EQUIDAD.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Melanoma in Solid Organ Transplant Recipients. / Melanoma en pacientes receptores de un trasplante de órgano sólido.

In this review, we analyze the 3 clinical scenarios related to the development of melanoma in solid organ transplant recipients: melanoma in patients with a history of the tumor prior to a transplant, de novo melanoma following a transplant, and melanoma of donor origin. The main factors to consider in organ-transplant candidates with a history of melanoma are tumor stage, presence or absence of residual disease, and time from diagnosis to transplantation. Solid organ transplant recipients have a greater risk of melanoma than immunocompetent individuals. Mortality is also higher in this population, especially in patients with advanced melanoma, as treatment is especially challenging. Clinical history and physical examination provide the most useful information for preventing donor-to-recipient transmission of melanoma. Donor-derived melanoma has a very poor prognosis.

Anticoagulantes orales directos en cirugía dermatológica / Direct-acting Oral Anticoagulants in Dermatologic Surgery

Los anticoagulantes orales directos (ACOD) emergen como una alternativa más cómoda y segura que los clásicos antagonistas de la vitamina K (AVK); no precisan monitorización, poseen una ventana terapéutica más amplia y tienen menos interacciones farmacológicas. Sin embargo, a pesar de que su uso está cada vez más extendido, existe poco consenso sobre cuál es su manejo perioperatorio óptimo en cirugía dermatológica. En este artículo se describen las características de los ACOD y se revisa la evidencia disponible sobre su uso perioperatorio en la cirugía de la piel

Direct-acting oral anticoagulants (DOACs) have emerged as safer, easier-to-manage alternatives to traditional vitamin K antagonists and are used increasingly because they require no monitoring, have a wider therapeutic window, and react less with other drugs. However, there is little consensus on optimal perioperative management when these drugs are used in dermatologic surgery. This article describes the characteristics of DOACs and reviews current evidence on their use in this setting

Direct-acting Oral Anticoagulants in Dermatologic Surgery. / Anticoagulantes orales directos en cirugía dermatológica.

Direct-acting oral anticoagulants (DOACs) have emerged as safer, easier-to-manage alternatives to traditional vitamin K antagonists and are used increasingly because they require no monitoring, have a wider therapeutic window, and react less with other drugs. However, there is little consensus on optimal perioperative management when these drugs are used in dermatologic surgery. This article describes the characteristics of DOACs and reviews current evidence on their use in this setting.

Pápulas faciales induradas / Indurated Papules on the Face

No disponible

Inmunoterapia en cáncer cutáneo no melanoma / Immunotherapy in Nonmelanoma Skin Cancer

La inmunoterapia en el cáncer emerge como un tratamiento novedoso y prometedor en una gran variedad de tumores, incluido el cáncer cutáneo no melanoma. Los anticuerpos inhibidores de proteínas de control inmunitario están dirigidos fundamentalmente a las moléculas de superficie CTLA-4 (antígeno citotóxico de los linfocitos T) y PD-1 (molécula de muerte programada 1). En el presente artículo se revisan las vías de CTLA-4 y PD-1/PD-L1 (PD-1/ligando de la PD-1) y las evidencias actuales de tratamiento con inhibidores de puntos de control inmunitario en los principales tipos de cáncer cutáneo no melanoma

Immunotherapy is emerging as a new and promising treatment for a great variety of tumors, including nonmelanoma skin cancer. Checkpoint inhibitors -antibodies that block proteins that regulate the immune system- mainly target the surface protein CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4) and the PD-1/PD-L1 (programmed cell death protein 1/PD-ligand 1) axis. We review the CTLA-4 and PD-1/PD-L1 pathways and current evidence supporting checkpoint inhibitor therapy in the main types of nonmelanoma skin cancer

Immunotherapy in Nonmelanoma Skin Cancer. / Inmunoterapia en cáncer cutáneo no melanoma.

Immunotherapy is emerging as a new and promising treatment for a great variety of tumors, including nonmelanoma skin cancer. Checkpoint inhibitors -antibodies that block proteins that regulate the immune system- mainly target the surface protein CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4) and the PD-1/PD-L1 (programmed cell death protein 1/PD-ligand 1) axis. We review the CTLA-4 and PD-1/PD-L1 pathways and current evidence supporting checkpoint inhibitor therapy in the main types of nonmelanoma skin cancer.

Experimental Infection of Domestic Pigs with African Swine Fever Virus Lithuania 2014 Genotype II Field Isolate.

An experimental infection was conducted to evaluate horizontal transmission, clinical, virological and humoral response induced in domestic pigs infected with African swine fever (ASF) genotype II virus circulating in 2014 into the European Union (EU). Ten naive pigs were placed in contact with eight pigs experimentally inoculated with the Lithuanian LT14/1490 ASF virus (ASFV) responsible for the first ASF case detected in wild boar in Lithuania in January 2014. Clinical examination and rectal temperature were recorded each day. Blood sampling from every animal was carried out twice weekly. Blood samples were examined for presence of ASF virus-specific antibodies and for determining the ASFV viral load. From the obtained results, it was concluded that the Lithuanian ASFV induced an acute disease which resulted in 94, 5% mortality. The disease was easily detected by real-time PCR prior to the onset of clinical signs and 33% of the animals seroconverted. All findings were in accordance with observations previously made in domestic pigs and wild boar when infected with ASF genotype II viruses characterized by a high virulence. One in-contact pig remained asymptomatic and survived the infection. The role of such animals in virus transmission would need further investigation.

Experimental Transmission of African Swine Fever (ASF) Low Virulent Isolate NH/P68 by Surviving Pigs.

African swine fever (ASF) has persisted in Eastern Europe since 2007, and two endemic zones have been identified in the central and southern parts of the Russian Federation. Moderate- to low-virulent ASF virus isolates are known to circulate in endemic ASF-affected regions. To improve our knowledge of virus transmission in animals recovered from ASF virus infection, an experimental in vivo study was carried out. Four domestic pigs were inoculated with the NH/P68 ASF virus, previously characterized to develop a chronic form of ASF. Two additional in-contact pigs were introduced at 72 days post-inoculation (dpi) in the same box for virus exposure. The inoculated pigs developed a mild form of the disease, and the virus was isolated from tissues in the inoculated pigs up to 99 dpi (pigs were euthanized at 36, 65, 99 and 134 dpi). In-contact pigs showed mild or no clinical signs, but did become seropositive, and a transient viraemia was detected at 28 days post-exposure (dpe), thereby confirming late virus transmission from the inoculated pigs. Virus transmission to in-contact pigs occurred at four weeks post-exposure, over three months after the primary infection. These results highlight the potential role of survivor pigs in disease maintenance and dissemination in areas where moderate- to low-virulent viruses may be circulating undetected. This study will help design better and more effective control programmes to fight against this disease.

Molecular typing of Streptococcus suis isolates from Iberian pigs: a comparison with isolates from common intensively-reared commercial pig breeds.

The Iberian pig (IP) is a traditional Spanish breed variety of the domestic pig (Sus scrofa domesticus) with high economic importance because of the value of the dry-cured products in national and international markets. The genetic characteristics of tonsillar and clinical Streptococcus suis isolates from the IP maintained under extensive or intensive management conditions were investigated. S. suis isolates from IP pigs were compared with S. suis isolates from intensively-farmed pigs of common breeds (CBP). S. suis was isolated from 48.4% of the IP tonsils examined, indicating wide distribution among IP pigs. Serotypes 1 (9.4%), 2 (8.6%) and 9 (7%) were the most commonly found, although a high percentage of S. suis isolates were not typeable by coagglutination testing. No significant differences in carrier rates or serotype diversity were observed between management systems, indicating that intensive farming does not influence S. suis colonisation. Both pulsed-field gel electrophoresis and multiple-locus variable number tandem repeat analysis showed a serotype-based distribution of S. suis IP isolates. Serotypes 1 and 2 S. suis isolates were grouped in the same cluster, whereas isolates of serotypes 9 and 7 were assigned to another cluster. All clinical and most tonsillar serotype 2 IP isolates were assigned to sequence type 1 (ST1) and exhibited the virulence genotype mrp+/epf+/sly+, indicating a high distribution of this genetic lineage among IP as well as a population of serotype 2 common to IPs and CBPs. The only clinical isolate of serotype 9 from IP was assigned to ST123, a sequence type associated with clinical isolates in CBPs in Spain.

Genetic analysis of Streptococcus suis isolates from wild rabbits.

This work aims to investigate the presence of Streptococcus suis in wild rabbits. A total of 65 S. suis isolates were recovered from 33.3% of the wild rabbits examined. Most isolates (86.2%) belong to genotype cps9. These isolates were further characterized by pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and virulence genotyping. Overall, S. suis exhibited a low genetic diversity. Only 5 genetic profiles were obtained by PFGE and most isolates (71.4%) were included in two pulsotypes that were also widely distributed among the wild rabbit population. MLST analysis assigned all cps9 isolates into three new singlestones (ST216, ST217 and ST284), which were not genetically related to the European ST87 and Spanish ST61 widespread swine clones, indicating a different genetic background for the S. suis isolates from wild rabbits and pigs. Wild rabbit isolates exhibited the genotype mrp-/epf-/sly-, different from those showed by most of the swine S. suis isolates of the ST87 and ST61 clones. None of the S. suis isolated from wild rabbits exhibited the genotype cps2/mrp+/epf+/sly+ associated with human infections. These results indicate that S. suis isolates from wild rabbits are not genetically related with prevalent clones usually associated with infections in pigs or humans in Europe and do not exhibit either their virulence genotypes. Therefore, although wild rabbits could represent an unknown reservoir of this pathogen, they could not represent a potential risk for pigs or humans.

Drying eggs to inhibit bacteria: Incubation during laying in a cavity nesting passerine.

Early incubation has been suggested as a defensive adaptation against potentially pathogenic bacteria colonizing avian eggshells in the wild. The inhibitory mechanisms underlying this adaptation are poorly understood and only recent experimental evidence demonstrates that keeping eggs dry is a proximate mechanism for the antimicrobial effects of avian incubation. We estimated partial incubation (the bouts of incubation that some birds perform during the egg-laying period, days of lay 3-5 in our population) intensity of female pied flycatchers breeding in nest-boxes using data loggers that allowed a precise measurement of temperature just between the eggs in the nest-cup. We also measured relative humidity within the nest-boxes and related it to incubation intensity, showing that more intense incubation during laying contributes to drying the air near the eggs. We analyzed separately the effects of incubation and of relative humidity on loads of three types of culturable bacteria known to be present on eggshells, heterotrophic bacteria, Gram-negative enterics and pseudomonads. Our results show an association of early incubation with an inhibition of bacterial proliferation through a drying effect on eggshells, as we found that incubation intensity was negatively and relative humidity positively associated with eggshell bacterial loads for heterotrophic bacteria, Gram-negative bacteria and pseudomonads, although the significance of these associations varied between bacterial groups. These results point to microclimatically driven effects of incubation on bacterial proliferation on eggshells during laying in a temperate cavity nesting passerine.

[Design and validation of a questionnaire to measure treatment satisfaction in patients with moderate-to-severe psoriasis: the NEODERMA study]. / Diseño y validación de un cuestionario para medir la satisfacción con el tratamiento del paciente con psoriasis moderada y grave: estudio NEODERMA.

BACKGROUND AND OBJECTIVES: the aim of this study was to design and assess the validity, reliability, and sensitivity to change of the Spanish Satisfaction With Treatment of Psoriasis Questionnaire (SSTPQ) for use in patients with moderate-to-severe psoriasis. PATIENTS AND METHODS: a prospective, multicenter, observational, naturalistic study was designed. The instrument consisted of 12 items scored on a 5-point Likert scale with scores from 0 (very satisfied) to 5 (very unsatisfied), generating a total score of 0 to 48. Patients completed the questionnaire at baseline and then at 3-, 6-, 9-, and 12-month follow-up. At each visit, data were also collected on the Psoriasis Area and Severity Index (PASI), treatment adherence (Morisky-Green questionnaire), and overall treatment satisfaction on a Visual Analogue Scale (VAS) from 0 to 100. RESULTS: a total of 423 patients were included in the study and 68% completed 12 months of follow-up. Responses were provided to all items in 98.8% of cases. There was a weak correlation between changes in treatment satisfaction on the SSTPQ and changes in PASI score (r = 0.38 to 0.33); in contrast, there were strong correlations with changes in the VAS score for overall treatment satisfaction (r = -0.75 to -0.81). Good internal consistency was observed (Cronbach α = 0.92). The intraclass correlation coefficient was 0.89, with a mean difference in score at 3- and 6-month follow-up of 0.07. CONCLUSIONS: The results obtained suggest that the SSTPQ is a feasible, valid, and reliable tool for the assessment of treatment satisfaction in patients with moderate-to-severe psoriasis.

Diseño y validación de un cuestionario para medir la satisfacción con el tratamiento del paciente con psoriasis moderada y grave: estudio NEODERMA / Design and Validation of a Questionnaire to Measure Treatment Satisfaction in Patients With Moderate-to-Severe Psoriasis: the NEODERMA Study

Introducción y objetivos: el objetivo del estudio fue diseñar y evaluar la validez, fiabilidad y sensibilidad al cambio de un cuestionario de satisfacción del tratamiento para el paciente con psoriasis moderada y grave, denominado CESTEP (Cuestionario Español de Satisfacción de Tratamiento en Psoriasis). Pacientes y métodos: se diseñó un estudio observacional, prospectivo, naturalístico y multicéntrico. El cuestionario estaba formado por 12 ítems, cada uno de los cuales se valoraba con una escala de tipo Likert con respuestas puntuables de 0 (muy satisfecho) a 5 (muy insatisfecho) (puntuación total de 0 a 48). Los pacientes cumplimentaron el cuestionario de satisfacción en la visita basal y a los 3, 6, 9 y 12 meses de seguimiento. En cada visita se recogieron también las variables clínicas (índice PASI), la adherencia con el tratamiento (cuestionario Morisky-Green) y la valoración global de la satisfacción con el tratamiento mediante una escala analógica visual (EAV) de 0 a 100. Resultados: se incluyeron un total de 423 pacientes, de los cuales el 68% finalizaron los 12 meses de seguimiento. El 98,8% de los pacientes completaron todas las preguntas del cuestionario. Los cambios en el cuestionario de satisfacción y en el índice PASI durante el estudio se correlacionaron de manera baja (r de 0,38 a 0,33), pero se observaron, en cambio, correlaciones altas con los cambios en la EAV de satisfacción (r de –0,75 a –0,81). Se obtuvo una buena consistencia interna (α de Cronbach de 0,92). El coeficiente de correlación intraclase era de 0,89, con una diferencia media en las puntuaciones, entre la visita a los 3 meses y a los 6 meses de 0,07 puntos. Conclusiones: los resultados obtenidos indican que el cuestionario CESTEP para la evaluación de la satisfacción del tratamiento en pacientes con psoriasis moderada y grave puede ser utilizado para tal finalidad, ya que se ha mostrado factible, válido y fiable (AU)

Background and objectives: the aim of this study was to design and assess the validity, reliability, and sensitivity to change of the Spanish Satisfaction With Treatment of Psoriasis Questionnaire (SSTPQ) for use in patients with moderate-to-severe psoriasis. Patients and methods: a prospective, multicenter, observational, naturalistic study was designed. The instrument consisted of 12 items scored on a 5-point Likert scale with scores from 0 (very satisfied) to 5 (very unsatisfied), generating a total score of 0 to 48. Patients completed the questionnaire at baseline and then at 3-, 6-, 9-, and 12-month follow-up. At each visit, data were also collected on the Psoriasis Area and Severity Index (PASI), treatment adherence (Morisky-Green questionnaire), and overall treatment satisfaction on a Visual Analogue Scale (VAS) from 0 to 100. Results: a total of 423 patients were included in the study and 68% completed 12 months of follow-up. Responses were provided to all items in 98.8% of cases. There was a weak correlation between changes in treatment satisfaction on the SSTPQ and changes in PASI score (r=0.38 to 0.33); in contrast, there were strong correlations with changes in the VAS score for overall treatment satisfaction (r=–0.75 to –0.81). Good internal consistency was observed (Cronbach α=0.92). The intraclass correlation coefficient was 0.89, with a mean difference in score at 3- and 6-month follow-up of 0.07. Conclusions: The results obtained suggest that the SSTPQ is a feasible, valid, and reliable tool for the assessment of treatment satisfaction in patients with moderate-to-severe psoriasis (AU)

[Long term efficacy and safety of etanercept in psoriasis]. / Eficacia y seguridad a largo plazo de etanercept en la psoriasis.

There are many studies that have shown that etanercept is an effective and safe drug for the short-term treatment of moderate to severe psoriasis. However, psoriasis is a disease with a chronic or recurrent course associated to arthritis and comorbidities that diminish the patient's health and quality of life and that often requires either continuous or intermittent long-term treatment. The data available on the use of etanercept in the long-term treatment of psoriasis, even at high doses, have shown that it has a good efficacy and safety profile. Half of the patients obtained a 75% improvement on the Psoriasis Area and Severity Index (PASI-75 during prolonged treatments of up to 96 months. The PASI 75 response is higher in continuous regimes than in intermittent ones (with pauses). Most of the patients maintain the response at long-term, although a decrease in efficacy is observed in some of them, as occurs with other tumor necrosis factor inhibitors. Accumulated experience with etanercept in other chronic inflammatory diseases also supports this good safety profile.

Eficacia y seguridad a largo plazo de etanercept en la psoriasis / Long term efficacy and safety of etanercept in psoriasis

Existen numerosos estudios que demuestran que etanercept es un medicamento eficaz y seguro para el tratamiento de la psoriasis moderada a grave a corto plazo. Sin embargo, la psoriasis es una enfermedad con curso crónico o recurrente, asociada a artritis y comorbilidades que merman la salud y la calidad de vida de los pacientes, requiriendo a menudo tratamiento a largo plazo, ya sea de forma continua o intermitente. Los datos disponibles sobre el empleo de etanercept como tratamiento de la psoriasis a largo plazo, incluso en dosis altas, demuestran un buen perfil de eficacia y seguridad. La mitad de los pacientes obtienen una mejoría PASI (Psoriasis Area and Severity Index) 75 durante tratamientos prolongados hasta 96 meses. La respuesta PASI 75 es superior en pautas continuas que en pautas intermitentes (con pausas). La mayoría de los pacientes mantienen la respuesta a largo plazo, aunque en algunos se observa una disminución de la eficacia, como ocurre con otros inhibidores del factor de necrosis tumoral. La experiencia acumulada con etanercept en otras enfermedades inflamatorias crónicas también respalda este buen perfil de seguridad (AU)

There are many studies that have shown that etanercept is an effective and safe drug for the short-term treatment of moderate to severe psoriasis. However, psoriasis is a disease with a chronic or recurrent course associated to arthritis and comorbidities that diminish the patient's health and quality of life and that often requires either continuous or intermittent long-term treatment. The data available on the use of etanercept in the long-term treatment of psoriasis, even at high doses, have shown that it has a good efficacy and safety profile. Half of the patients obtained a 75% improvement on the Psoriasis Area and Severity Index (PASI-75 during prolonged treatments of up to 96 months. The PASI 75 response is higher in continuous regimes than in intermittent ones (with pauses). Most of the patients maintain the response at long-term, although a decrease in efficacy is observed in some of them, as occurs with other tumor necrosis factor inhibitors. Accumulated experience with etanercept in other chronic inflammatory diseases also supports this good safety profile (AU)