[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.

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study. / [Artículo traducido] Sonidegib para el tratamiento del carcinoma basocelular avanzado en práctica clínica real: estudio nacional multicéntrico.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24 h and 48 h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24h and 48h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.

Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV): Data for the First 5 Years. / Registro de linfomas cutáneos primarios (RELCP) de la AEDV: datos tras 5 años de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years. PATIENTS AND METHODS: RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years. RESULTS: Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]). CONCLUSION: The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data.

Percutaneous radiofrequency for the treatment of small renal masses: Analysis of outcomes and complications after 10 years of experience. / Radiofrecuencia percutánea en el tratamiento de masas renales pequeñas: análisis de resultados y complicaciones tras diez años de experiencia.

INTRODUCTION AND OBJECTIVE: The management of renal tumors ≤ 4 cm in elderly population or patients with comorbidities is a challenge, for which ablative therapies are an interesting alternative. The objective is to evaluate in our center the role of percutaneous radiofrequency in the treatment of small renal masses, the associated complications and the results obtained. MATERIAL AND METHODS: Retrospective evaluation of the radiofrequency treatments carried out between April 2010 and April 2020 in our center. Demographic data, associated comorbidities, tumor characteristics, complications and oncological and functional outcomes were reviewed. RESULTS: Fifty-seven tumors were treated in 53 patients. Mean follow-up of 48.2 months. The percentage of complete ablations obtained was of 89.5%. There were 19.3% of complications. According to Clavien-Dindo and SIR classification systems, 3.5% and 5.3% were major complications. A statistically significant association was found between the initial result of ablation and age (p = 0.047), RENAL-m (p = 0.044), the presence of cystic component (p = 0.049) and tumor size (p = 0.01). The cut-off point for size was established at 25 mm (p = 0.012). In multivariate analysis, only size remained as a predictor of initial ablation result (p = 0.01; OR 1.183; CI 95% 1.041-1.345). Cancer-specific survival and 5-year recurrence-free survival were 98.1% and 89.5%, respectively. A mean decrease of MDRD-4 of 6.59 mL/min (p = 0.005) was observed in the first six months after RFA. CONCLUSIONS: Given the excellent oncological and functional results demonstrated, ultrasound-guided percutaneous radiofrequency ablation is an effective and safe treatment for small renal masses in selected patients.

Dermatoscopic features of thin (≤2 mm Breslow thickness) vs. thick (>2 mm Breslow thickness) nodular melanoma and predictors of nodular melanoma versus nodular non-melanoma tumours: a multicentric collaborative study by the International Dermoscopy Society.

BACKGROUND: Thin nodular melanoma (NM) often lacks conspicuous melanoma-specific dermatoscopic criteria and escapes clinical detection until it progresses to a thicker and more advanced tumour. OBJECTIVE: To investigate the dermatoscopic morphology of thin (≤2 mm Breslow thickness) vs. thick (>2 mm) NM and to identify dermatoscopic predictors of its differential diagnosis from other nodular tumours. METHODS: Retrospective, morphological case-control study, conducted on behalf of the International Dermoscopy Society. Dermatoscopic images of NM and other nodular tumours from 19 skin cancer centres worldwide were collected and analysed. RESULTS: Overall, 254 tumours were collected (69 NM of Breslow thickness ≤2 mm, 96 NM >2 mm and 89 non-melanoma nodular lesions). Light brown coloration (50.7%) and irregular brown dots/globules (42.0%) were most frequently observed in ≤2 mm NMs. Multivariate analysis revealed that dotted vessels (3.4-fold), white shiny streaks (2.9-fold) and irregular blue structureless area (2.4-fold) were predictors for thinner NM compared to non-melanoma nodular tumours. Overall, irregular blue structureless area (3.4-fold), dotted vessels (4.6-fold) and serpentine vessels (1.9-fold) were predictors of all NM compared to non-melanoma nodular lesions. LIMITATIONS: Absence of a centralized, consensus pathology review and cases selected form tertiary centres maybe not reflecting the broader community. CONCLUSIONS: Our study sheds light into the dermatoscopic morphology of thin NM in comparison to thicker NM and could provide useful clues for its differential diagnosis from other non-melanoma nodular tumours.

0.5% 5-Fluorouracil/10% Salicylic Acid for the Treatment of Distal Actinic Keratoses Under Daily Practice Conditions

Background: Actinic keratosis (AKs) are sun-induced skin lesions that are at risk to progress to invasive squamous cell carcinoma (SCC). Treatments have shown to be effective on face or balding scalp area but limited data support their efficacy on distal extremities. Objective: To describe the efficacy of 0.5% 5-fluorouracil/10% salicylic acid (5FU/AS) in the treatment of distally-located AKs in daily clinical practice. Additional objectives were to review tolerance and adherence to this treatment. Methods: Retrospective review of 23 patients with distal grade II to III AKs who were treated with 5FU/AS under daily practice conditions. Primary endpoint included local skin response according to percentage on AKs reduction at week 20 (8 weeks after ending the treatment). Results: 75% (30/40) treatment areas showed a percentage reduction in AKs from to 75% to 100% at week 20. Complete response (100% clearance) was recorded in more than half of the cases (53%, 21/40). Good, partial, and low responses were respectively observed in 22% (9/40), 20% (8/40), and 5% (2/40) of patients. Most adverse events were graded as low, and adherence to treatment was considered correct in 25 patients (63%). In addition, a correct adherence to treatment was significantly related to a better response (P=0.001). Conclusion: Findings indicate that topical 5FU/AS is an effective treatment for multiple distal AKs, with a proper safety profile. J Drugs Dermatol. 2019;18(3):285-288.

The First Year of the AEVD Primary Cutaneous Lymphoma Registry. / Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. PATIENTS AND METHODS: Disease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. RESULTS: In December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30+ T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical corticosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). CONCLUSION: The characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group.

Clinical Response to Ingenol Mebutate in Patients With Actinic Keratoses.

Cryotherapy is the most common treatment for actinic keratosis, but its effect is limited to individual lesions. Several topical drugs, however, are available that, in addition to treating individual actinic keratoses, target field cancerization and thereby act on subclinical lesions. Examples are 5-fluorouracil, imiquimod, diclofenac, and ingenol mebutate. We report on 17 patients with actinic keratoses treated with ingenol mebutate and describe our findings on treatment effectiveness, adherence, and tolerance. Complete and partial response rates were 35% and 53%, respectively. Ninety-four percent of patients fully adhered to treatment and 18% developed severe local reactions. Ingenol mebutate is an effective treatment for actinic keratosis. Although it has a similar rate of local reactions to other treatments available for actinic keratosis, its short treatment regimen favors better adherence.

Preoperative levosimendan. A new way for organoprotection.

Preoperative use of levosimendan in cardiac surgery patients is one of the most attractive therapeutic alternatives in subjects with left or right ventricular dysfunction. Our review explores the pharmacological bases and clinical evidence for the use of levosimendan, with the intention of making a series of recommendations regarding its use in preoperative optimization prior to cardiac surgery. We carried out a survey of 102 Spanish anesthesiologists in order to shed light on the grey areas regarding the use of this drug prior to surgery. Our findings suggest that levosimendan is recommended for patients with severe left or right ventricular dysfunction, moderate left ventricular dysfunction in which Intra-aortic Balloon Counterpulsation (IABC) is necessary and severe pulmonary hypertension. Administration of levosimendan prior to surgical cardiac intervention without an initial bolus reduces the likelihood of complications.

Analysis of vascular endothelial growth factor gene expression in the tissues of patients with chronic venous insufficiency.

OBJECTIVE: Immunohistochemical techniques have revealed the presence of vascular endothelial growth factor (VEGF) in the epidermis of patients with chronic venous disease (CVD). Our objective was to perform a quantitative analysis of the VEGF gene transcription in tissues that are potential sources of this factor (skin, varicose veins [VV] and great saphenous vein [GSV]) in patients with CVD. METHODS: In all, 212 skin and venous tissue samples were collected from patients diagnosed with CVD and controls. The VEGF gene expression was analysed using quantitative realtime polymerase chain reaction (PCR). RESULTS: The skin VEGF expression was lower in the CVD group than in the control group (P = 0.04). There were no significant differences between the insufficient GSV of the CVD group and the control healthy vein (P = 0.22). There was a greater expression of VEGF in the VV of the CVD group than in the control healthy vein (P = 0.03). Comparison of the VEGF expression between the different tissue types in the CVD group revealed significant differences between the skin and GSV (P = 0.02) and between the skin and the VV (P = 0.004), and between the VV and the GSV (P = 0.02). CONCLUSIONS: The results of the present study show an over-expression of VEGF gene in the VV tissue of patients with CVD. Based on the data in patients with C2 disease, the VVs appear to be the source of increased VEGF expression.

Nevus oligemicus: a case series.

BACKGROUND: Nevus oligemicus is a functional nevus caused by vasoconstriction of the cutaneous deep vascular plexus, and vasodilatation of vessels of the superficial dermis due to abnormal responses of adrenergic receptors. To the best of our knowledge, only 14 cases in 8 articles were reported in the revised indexed literature. Case report We present five cases of nevus oligemicus in two males and in three female patients. Common characteristics in all patients were overweight and sedentary habits. DISCUSSION: Nevus oligemicus is an uncommon condition characterized by livid and cyanotic patches with localized hypothermia as the key-diagnostic sign. It has been suggested that this entity is probably underdiagnosed, as it is asymptomatic and remains stable in its evolution.