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.

[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.

[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.

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.

[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.

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.

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.

Revision of the antigenic structure of genus Listeria.

O-antigenic structure of genus Listeria was studied, using antisera (obtained from rabbits) against different O-antigens of reference strains of each serovar. The titres of sera were determined by agglutination using antigens of the same reference strains as well. Some differences from the actual scheme were found: serum antifactor-IX gave a lower titre than expected against antigens 4ab and 6b, while the titre observed against antigen 4b was higher than the expected in this case. Serum antifactor-VIII presented a higher titre than could be expected against antigen 6b. The strains of serovars 4d and 4e used in this experience were impossible to distinguish, and could have been classified in the same serovar. We could not obtain serum antifactor-XI from serovar 6b after several trials. From these differences we propose some modifications of the current antigenic scheme of genus Listeria.

Serological response in rabbits to Listeria monocytogenes after oral or intragastric inoculation.

The serological response in rabbits against Listeria monocytogenes after oral or intragastric inoculation was investigated. Both the number of sero-positive animals and the average serum titres were higher in animals inoculated by the oral route. This difference was especially marked in rabbits inoculated with the lower dose (1 x 10(3) colony-forming units (cfu)), which developed a strong serological response (average serum titre of 1280 after 4 inoculations) in most of the inoculated animals (80%), without any clinical signs. The implication of these results in the epidemiology of listeriosis is discussed.

Prolonged persistence of Listeria monocytogenes after intragastric infection in corticosteroid-treated mice.

In an attempt to obtain a model more closely resembling natural listeriosis, we studied the course of infection in mice inoculated by the intragastric route with Listeria monocytogenes. Corticosteroid-treated, and untreated mice both developed subclinical infection without mortality, but faecal shedding and persistence of bacteria in the liver and spleen of corticosteroid-treated mice were significantly more protracted than in untreated mice. Untreated mice cleared the bacteria from their livers and spleens by day 5 postinfection (PI), whereas treated mice did not clear the organisms until 8-9 days PI. In untreated mice faecal shedding lasted 5 days PI, whereas in treated mice the organisms were recovered at significantly higher levels until day 9 PI. The only intestinal lesions observed were mild pyogranulomatous changes in the dome area of some Peyer's patches in treated mice.

Beak infection by Penicillium cyclopium in a macaw (Ara ararauna).

A case of localized beak infection by Penicillium cyclopium in a macaw (Ara ararauna) is described. A necrotic lesion, with destruction of the corneous layer, was localized in the upper zone of the beak. Diagnosis was carried out on samples of the affected zone by direct microscopic observation, routine fungal culturing techniques, and scanning electron microscopy. Results were consistent: P. cyclopium was the only microorganism associated with the lesion site. No previous reports concerning this type of beak pathology have been found in the literature.

Metastatic Listeria monocytogenes infection of the peritoneum in mice with cyclosporine a-induced peritonitis.

Inoculation of mice with Listeria monocytogenes intragastrically or by parenteral routes has not been reported to cause peritonitis. In this study, however, severe listerial peritonitis was induced in mice infected subcutaneously and treated intraperitoneally with cyclosporin A (Cs A) in an oil carrier. In both uninfected and listeria-infected mice, intraperitoneal administration of Cs A consistently produced overexpression of P-selectin in the peritoneal microvasculature and pyogranulomatous inflammation of the peritoneum, suggesting that Cs A causes endothelial damage. We suggest that in listeria-infected mice the non-specific irritant peritonitis induced by the intraperitoneal administration of Cs A results in transfer of listeria-infected phagocytes from the liver and spleen to the peritoneal microvasculature, producing metastatic infection.

A microbiological, histopathological and immunohistological study of the intragastric inoculation of Listeria monocytogenes in mice.

The course of murine infection after intragastric inoculation of L. monocytogenes was investigated by immunocytochemical, histopathological and microbiological techniques. L. monocytogenes antigen was observed in epithelial cells of intestinal mucosa overlying Peyer's patches, but not in mucosa devoid of them. This suggests that penetration of L. monocytogenes into the host organism may take place through epithelium overlying Peyer's patches. The efficiency of bacterial penetration appeared to be low, as shown by the small amounts of L. monocytogenes antigen detected and the low counts of bacteria in organs. Gross or histopathological lesions in the intestinal tract were not observed. The presence of L. monocytogenes in spleen, liver and in maxillary and mesenteric lymph nodes, confirmed that the systemic course of infection by this route of inoculation is similar to that of the parenteral routes. The results emphasize the subclinical character of murine listeriosis by the oral route.

Pathogenesis of lymphoid lesions in murine experimental listeriosis.

Adult female Swiss albino mice were infected intraperitoneally or subcutaneously with Listeria monocytogenes Serovar 4b or 1/2a and killed at intervals. Thymus, spleen, Peyer's patches and a variety of lymph nodes, including the jejunal (mesenteric), mediastinal, lumbar, mandibular and superficial inguinal, were examined by histopathology and by immunocytochemistry for detection of L. monocytogenes antigen. Similar results were obtained with both Serovars and by both routes of inoculation used. In the spleen, L. monocytogenes was detected, by immunoperoxidase staining, as soon as 4 h after inoculation, inside phagocytic cells located predominantly in the marginal zone of the white pulp. This was followed by inflammation, necrosis and depletion of lymphoid cells, which extended in extreme cases to the whole organ. Inflammatory lesions diminished progressively at 5 to 6 days after inoculation. In animals dying of the infection, a severe necrotizing splenitis was present. Depletion of lymphoid cells and inflammatory changes were widespread in the lymph nodes and to a lesser extent in the Peyer's patches. An extensive necrotizing lymphadenitis was the prominent lesion in severely affected nodes. Inflammatory lesions and detection of L. monocytogenes antigen started around the venules of high endothelium. A thymus depletion, not associated with the multiplication of bacteria in the organ, was also a constant feature of the infection. This study suggests that L. monocytogenes (1) is transported to the spleen and to the lymph nodes by phagocytes, entering the organs by the marginal sinus in the spleen and by the venules of high endothelium in the lymph nodes; (2) multiplies in these cells as well as in neutrophilic granulocytes (the latter rapidly migrate to the affected zones); and (3) induce a splenitis and lymphadenitis, involving predominantly T cell-dependent areas, with a necrotizing component in severe cases. From our observations it is concluded that infection of the lymphoid system is a major feature in the pathogenesis of murine listeriosis.

Repeated oral dosing with Listeria monocytogenes in mice as a model of central nervous system listeriosis in man.

Human listeriosis is a food-borne disease of immunosuppressed or previously healthy adults. The repeated oral administration of a sublethal dose (5x10(9)colony-forming units) of Listeria monocytogenes for 7 or 10 consecutive days led to the development of severe central nervous system (CNS) lesions in 25% of experimental mice. Histopathological examination of the brain revealed rhombencephalitis and ventriculitis as two distinct inflammatory patterns, resembling those seen in human listeriosis. This model would seem to be potentially useful for research on pathogenesis, predisposing factors and therapy in CNS listeriosis in man. 1999 W.B. Saunders and Company Ltd.

Effect of selenium deficiency on the development of central nervous system lesions in murine listeriosis.

The effect of selenium (Se) deficiency, produced by feeding a Se-deficient diet, on the development of central nervous system (CNS) lesions was studied in mice infected with Listeria monocytogenes, administered in drinking water for 1 or 7 days in a daily dose of 10(9)organisms, or for 7 days in a daily dose of 10(7). Se-deficient mice differed from Se-normal controls in developing CNS lesions significantly more frequently. Moreover, regardless of Se status, mice receiving repeated doses of 10(9)organisms differed from those receiving a single 10(9)dose in showing CNS lesions at least twice as often. The majority of animals with CNS lesions showed an inflammatory pattern of rhombencephalitis (17/24), while only two of 24 showed choroiditis-ventriculitis-meningitis; five of 24 animals showed both inflammatory patterns. Listeria monocytogenes antigen was identified within the areas of inflammation by an immunoperoxidase technique. Neuritis of the trigeminal nerve was present in eight animals. The relative lack of pathological changes in the liver and spleen validates this murine model for the study of CNS listeriosis.