[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.

Clinical and ultrasound response to intralesional sodium thiosulfate for the treatment of calcinosis cutis in the setting of systemic sclerosis. A case-based review.

Calcinosis cutis (CC) is defined as the deposition of calcium salts on the skin and subcutaneous tissue. It is associated with different conditions, including some autoimmune diseases, and it can generate significant inflammation, pain, and functional impairment. Different therapies have been tried with limited results. Intralesional sodium thiosulfate seems a promising therapeutic option. We report a patient with diffuse systemic sclerosis who presented with two symmetrical plaques on both axillae, which caused pain and skin retraction. The clinical diagnosis was consistent with CC, which was confirmed by skin biopsy and ultrasound. The patient was treated with a 250 mg/ml solution of sodium thiosulfate injected into the plaques. Complete resolution was achieved after three monthly sessions. The only reported adverse effect was a transient burning sensation during the injections. Given its effectiveness and safety, we believe that intralesional sodium thiosulfate could become a valid first-line option for the treatment of CC.

Facial Angiofibroma Severity Index (FASI): reliability assessment of a new tool developed to measure severity and responsiveness to therapy in tuberous sclerosis-associated facial angiofibroma.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder characterized by the development of multisystem hamartomatous tumours. Topical sirolimus has recently been suggested as a potential treatment for TSC-associated facial angiofibroma (FA). AIM: To validate a reproducible scale created for the assessment of clinical severity and treatment response in these patients. METHODS: We developed a new tool, the Facial Angiofibroma Severity Index (FASI) to evaluate the grade of erythema and the size and extent of FAs. In total, 30 different photographs of patients with TSC were shown to 56 dermatologists at each evaluation. Three evaluations using the same photographs but in a different random order were performed 1 week apart. Test and retest reliability and interobserver reproducibility were determined. RESULTS: There was good agreement between the investigators. Inter-rater reliability showed strong correlations (> 0.98; range 0.97-0.99) with inter-rater correlation coefficients (ICCs) for the FASI. The global estimated kappa coefficient for the degree of intra-rater agreement (test-retest) was 0.94 (range 0.91-0.97). CONCLUSIONS: The FASI is a valid and reliable tool for measuring the clinical severity of TSC-associated FAs, which can be applied in clinical practice to evaluate the response to treatment in these patients.

Cutaneous adverse events associated with heparin.

Heparin use is associated with various cutaneous reactions, with the most common being immune-mediated skin lesions and bleeding complications. In this review, we compile the dermatological side-effects of heparin reported in the literature, and provide a clear approach to their adequate management.

Correlation of GREB1 mRNA with protein expression in breast cancer: validation of a novel GREB1 monoclonal antibody.

Studies of gene regulated by estrogen in breast cancer 1 (GREB1) have focused on mRNA levels with limited evidence about GREB1 protein expression in normal and breast cancer cells. A monoclonal antibody that recognizes GREB1 protein in breast tissues could be applied to correlate protein expression with established mRNA expression data. A hybridoma expressing a murine monoclonal antibody targeting a 119 amino acid peptide specific to human GREB1 was generated. The novel monoclonal GREB1 antibody (GREB1ab) was validated for use in Western blotting as well as immunohistochemical (IHC) applications. GREB1ab detects a 216 kDa protein corresponding to GREB1 in estrogen receptor alpha (ERalpha+) breast cancer cells as well as ERalpha- breast cancer cells transduced with a GREB1 expression vector. GREB1ab specificity was verified using an ERalpha antagonist to prevent GREB1 induction as well as a silencing siRNA targeting GREB1 mRNA. GREB1ab was further validated for detection of GREB1 by IHC in breast cancer cell lines and breast tissue microarrays (TMA). ERalpha+ cell lines were observed to express GREB1 while ERalpha- cell lines did not express detectable levels of the protein. Using breast cancer tissue whole sections, IHC with the GREB1ab identified protein expression in ERalpha+ breast cancer tissue as well as normal breast tissue, with little GREB1 expression in ERalpha- breast cancer tissue. Furthermore, these data indicate that GREB1 mRNA expression correlates well with protein expression. The novel monoclonal GREB1ab is specific for GREB1 protein. This antibody will serve as a tool for investigations focused on the expression, distribution, and function of GREB1 in normal breast and breast cancer tissues.

Case report: Liposarcoma of the sinonasal tract.

Nasal and paranasal malignant tumours account for less than 5% of all head and neck malignancies. Epithelial malignancies overwhelmingly predominate, with squamous cell carcinomas representing the most frequent histological subtype in this location. Soft-tissue sarcomas of the nasal cavity and paranasal sinuses are exceedingly rare. Here, we report two cases of myxoid liposarcomas that occurred in the nasal and paranasal regions, both of which presented diagnostic challenges and could not be diagnosed definitively from intraoperative frozen sections. These cases reinforce the notion that, while they are uncommon, sarcomas in general and liposarcomas in particular should still be considered as part of the differential diagnosis in patients presenting with obstructive symptoms in the nasal and paranasal sinuses.

[Duration of untreated psychosis as predictive and prognostic factor in the course of first episode psychosis]. / El tiempo de psicosis no tratada como factor predictivo y pronóstico en el curso de los primeros episodios psicóticos.

INTRODUCTION: Recently, many studies have focused on the duration of untreated psychosis (DUP) in order to clarify if DUP could be one of the factors that would influence prognosis of psychotic disease. MATERIAL AND METHODS: We present a one year follow - up study with 90 medication native, first episode psychotic patients. The likely prognosis factors that could influence in the outcome of the disease were measured. Therefore, we used a protocol including the following scales: PANSS, Psychosocial Stress Global Assessment scale (DSM IIIR), Global Assessment of Functioning scale (GAF-EEAG), Clinical Global Impression (CGI), Montgomery-Asberg scale for the depression, Young mania rating scale, abnormal involuntary movements scale, UKU scale for extrapyramidal symptoms and Premorbid Adjustment scale (Cannon-Spoor). Assessments were made every three months for 1 year. A statistical analysis of data was performed. RESULTS: As a result, it was concluded that there was no relationship between a long duration untreated psychosis and a worse outcome of the illness in our sample. The only related factors with the prognosis were premorbid adjustment and the type of disease onset. Hence, the patients with a better premorbid adjustment and an acute onset of psychosis had a better outcome. CONCLUSION: Our study represents more evidence in favor of the independence of DUP and disease outcome.

MUC4 (sialomucin complex) expression in salivary gland tumors and squamous cell carcinoma of the upper aerodigestive tract.

OBJECTIVES: This study investigates MUC4 expression in normal squamous epithelia and squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT), and in salivary gland neoplasms. STUDY DESIGN: MUC4 antigens in tumor and adjacent normal tissue are localized by immunocytochemical studies. Fresh frozen tissues from surgical resection specimens are further analyzed by Western blot. RESULTS: MUC4 is identified by immunocytochemical staining throughout the normal UADT mucosa, in 34 of 40 primary UADT SCC, and in 11 of 12 metastatic cervical lymph nodes. A trend toward decreased MUC4 staining in moderately and poorly differentiated tumors is noted. Immunoblots show MUC4 in 4 of 5 SCC analyzed. Immunocytochemical staining of MUC4 in 13 major and minor salivary gland neoplasms reveal variable staining of normal and neoplastic tissue. MUC4 is demonstrated in immunoblots of normal parotid tissue and in the single parotid malignancy analyzed, but is not demonstrated in one minor salivary gland malignancy. These findings characterize normal UADT mucosal and salivary MUC4 expression, and MUC4 expression in SCC of the UADT and in salivary gland tumors. SIGNIFICANCE: Correlation of MUC4 expression with clinical outcomes may establish MUC4 as a potential molecular prognostic marker for these tumors.

Breast cancer and human immunodeficiency virus: a report of 20 cases.

Carcinoma of the breast is the most common malignancy in women in the United States. More than 40% of patients with human immunodeficiency virus (HIV) infection develop cancer during their illness, but breast cancer has seldom been reported. Twenty patients with breast cancer and HIV infection seen at the University of Miami/Jackson Memorial Hospital between January 1988 and August 2000 were retrospectively analyzed. Seventeen patients had a previous or concurrent diagnosis of HIV at the time of the breast cancer diagnosis. Their CD4 count ranged from 13-1126/microL (median, 309/microL). Most patients were premenopausal (16 of 20), with ages ranging from 31-61 years (median, 44 years). All stages of breast cancer were seen: ductal carcinoma in situ (2 patients), stage I (1 patient), stage II (9 patients), stage III (6 patients), and stage IV (2 patients). Ten tumors had estrogen receptors. Four of the 13 patients who underwent axillary lymph node dissection had abnormal lymph node findings, including 2 with follicular hyperplasia and 2 with caseating granulomas. Seven patients received chemotherapy with very poor tolerance. Estrogen receptor-positive patients were treated with tamoxifen. Of the 18 patients who presented with local disease, 7 have died: 2 of breast cancer, 4 of acquired immunodeficiency syndrome, and 1 of cardiac arrest. Nine patients remain free of disease (5 of them > 5 years) and 2 patients are alive with metastatic disease. Breast cancer in the HIV-positive population is similar to that seen in seronegative women. Most of the patients that are long-term survivors were treated with surgery and tamoxifen. The benefits of adjuvant chemotherapy are not clear.

Normal endometrial cells in Papanicolaou smears: prevalence in women with and without endometrial disease.

OBJECTIVE: To determine whether the prevalence of normal endometrial cells in Papanicolaou smears of women with and those without endometrial carcinoma or hyperplasia differs significantly. METHODS: Papanicolaou smears of women with biopsy-proved endometrial hyperplasia or carcinoma diagnosed between 1990 and 1998 were reviewed for the presence of normal endometrial cells. Chi-square and a power analysis were used to compare these smears with results of smears from women older than 35 years of age with tissue diagnoses other than hyperplasia or carcinoma. All Papanicolaou smears obtained within the 5 years before endometrial sampling were reviewed. Each patient had at least one smear done within the previous 12 months. Clinical information was available for all patients. RESULTS: Of the 201 women in whom endometrial hyperplasia (n = 103) or carcinoma (n = 98) was diagnosed, 4 (2%) had normal endometrial cells in otherwise negative Papanicolaou smears. Of the 289 women in the comparison group, 15 (5%) had normal endometrial cells in their Papanicolaou smears. The prevalence of normal endometrial cells did not differ significantly between the two groups (P =.071). The study had 80% power to detect a 5% or greater difference between groups. CONCLUSION: The prevalence of normal endometrial cells in Papanicolaou smears of women with endometrial carcinoma or hyperplasia does not significantly differ from that in women without these conditions. Reporting normal endometrial cells in Papanicolaou smears according to the recommendations of the Bethesda System may lead to unnecessary procedures and patient anxiety.

Expression of GLUT-1 glucose transporter in borderline and malignant epithelial tumors of the ovary.

OBJECTIVE: Cancer cells have increased rates of glucose metabolism when compared to normal cells. One of the mechanisms proposed for the accelerated glucose use in malignant cells is the overexpression of glucose transporters. In this study we evaluated the expression of the GLUT-1 glucose transporter in borderline and malignant epithelial neoplasms of the ovary. METHODS: Histologic sections of tumor tissues from 21 borderline and 82 malignant epithelial neoplasms of the ovary were stained for GLUT-1 using polyclonal GLUT-1 antibody (Dako, Carpinteria, CA) and the labeled streptavidin biotin procedure. DAB was used as chromagen and tissues were counterstained with hematoxylin. RESULTS: Normal ovarian surface epithelial cells were either negative or weakly positive. Of the 82 carcinomas, 81 (98.8%) were positive for GLUT-1. The staining intensity was significantly associated with the grade of tumor (P = 0.001). Of the 21 borderline neoplasms, 20 (95.2%) were positive for GLUT-1. Carcinomas had a significantly stronger stain than borderline tumors (P = 0.0001). The intensity of the stain was also stronger in serous carcinomas compared to other subtypes (P = 0. 0001). Positive cells demonstrated a cytoplasmic membrane staining that was more intense in tumor cells farther away from blood supply. CONCLUSION: Overexpression of the GLUT-1 transporter is associated with the histology and grade of the tumors. Our findings show a progressive increase in the expression of the GLUT-1 transporter from the borderline tumor to the high-grade carcinomas. These data suggest that the expression of this transporter may be closely related to the malignant transformation of epithelial ovarian tumors.

Reporting normal endometrial cells in Pap smears: an outcome appraisal.

OBJECTIVE: The purpose of this study was to determine the clinical relevance of reporting the presence of normal endometrial cells in the Pap smears of women over the age of 35 years and the significance of this practice as it relates to patient management. METHODS: From January 1992 to December 1995, normal endometrial cells were reported in 206 consecutive Pap smears of women over the age of 35 years. Clinical follow-up was available for all patients, including the results of diagnostic procedures whenever performed. RESULTS: Of the 206 women with normal endometrial cells in their Pap smears, 162 presented with the chief complaint of abnormal vaginal bleeding. They were all evaluated by direct endometrial sampling, resulting in detection of 10 endometrial hyperplasias and 7 endometrial carcinomas. The remaining 44 women who were clinically asymptomatic were followed up with only routine annual gynecologic examinations for a minimum of 3 years. All had negative clinical courses. CONCLUSION: Reporting the presence of normal endometrial cells in Pap smears has little, if any, impact on subsequent patient management. Women who present with abnormal uterine bleeding are worked up for endometrial disease regardless of their Pap smear findings. In clinically asymptomatic patients, practitioners may, and in our experience often do, choose to disregard normal endometrial cells in Pap smear reports. The negative follow-up for the asymptomatic women in our study supports this practice. Therefore, reporting the presence of normal endometrial cells in Pap smears is of no clinical relevance and may, in fact, create a management dilemma for clinicians.

Metastatic medullary thyroid carcinoma in liver diagnosis by aspiration cytology.

A case of metastatic medullary thyroid carcinoma (MTC) to the liver of a patient with multiple endocrine neoplasia (MEN) Type IIb was suggested by percutaneous fine-needle aspiration cytology and confirmed by histology and immunohistochemistry. The cytologic presentation of this unusual thyroid cancer in liver has not been previously reported. We report such a case and discuss its differential diagnosis from other metastatic tumors of the liver.