Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain.

BACKGROUND: Brain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab in metastatic melanoma have excluded patients with untreated brain metastases. We evaluated the efficacy and safety of nivolumab plus ipilimumab in patients with melanoma who had untreated brain metastases. METHODS: In this open-label, multicenter, phase 2 study, patients with metastatic melanoma and at least one measurable, nonirradiated brain metastasis (tumor diameter, 0.5 to 3 cm) and no neurologic symptoms received nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for up to four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks until progression or unacceptable toxic effects. The primary end point was the rate of intracranial clinical benefit, defined as the percentage of patients who had stable disease for at least 6 months, complete response, or partial response. RESULTS: Among 94 patients with a median follow-up of 14.0 months, the rate of intracranial clinical benefit was 57% (95% confidence interval [CI], 47 to 68); the rate of complete response was 26%, the rate of partial response was 30%, and the rate of stable disease for at least 6 months was 2%. The rate of extracranial clinical benefit was 56% (95% CI, 46 to 67). Treatment-related grade 3 or 4 adverse events were reported in 55% of patients, including events involving the central nervous system in 7%. One patient died from immune-related myocarditis. The safety profile of the regimen was similar to that reported in patients with melanoma who do not have brain metastases. CONCLUSIONS: Nivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had untreated brain metastases. (Funded by Bristol-Myers Squibb and the National Cancer Institute; CheckMate 204 ClinicalTrials.gov number, NCT02320058 .).

Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis.

BACKGROUND: Obesity has been linked to increased mortality in several cancer types; however, the relation between obesity and survival outcomes in metastatic melanoma is unknown. The aim of this study was to examine the association between body-mass index (BMI) and progression-free survival or overall survival in patients with metastatic melanoma who received targeted therapy, immunotherapy, or chemotherapy. METHODS: This retrospective study analysed independent cohorts of patients with metastatic melanoma assigned to treatment with targeted therapy, immunotherapy, or chemotherapy in randomised clinical trials and one retrospective study of patients treated with immunotherapy. Patients were classified according to BMI, following the WHO definitions, as underweight, normal, overweight, or obese. Patients without BMI and underweight patients were excluded. The primary outcomes were the associations between BMI and progression-free survival or overall survival, stratified by treatment type and sex. We did multivariable analyses in the independent cohorts, and combined adjusted hazard ratios in a mixed-effects meta-analysis to provide a precise estimate of the association between BMI and survival outcomes; heterogeneity was assessed with meta-regression analyses. Analyses were done on the predefined intention-to-treat population in the randomised controlled trials and on all patients included in the retrospective study. FINDINGS: The six cohorts consisted of a total of 2046 patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy between Aug 8, 2006, and Jan 15, 2016. 1918 patients were included in the analysis. Two cohorts containing patients from randomised controlled trials treated with targeted therapy (dabrafenib plus trametinib [n=599] and vemurafenib plus cobimetinib [n=240]), two cohorts containing patients treated with immunotherapy (one randomised controlled trial of ipilimumab plus dacarbazine [n=207] and a retrospective cohort treated with pembrolizumab, nivolumab, or atezolizumab [n=331]), and two cohorts containing patients treated with chemotherapy (two randomised controlled trials of dacarbazine [n=320 and n=221]) were classified according to BMI as normal (694 [36%] patients), overweight (711 [37%]), or obese (513 [27%]). In the pooled analysis, obesity, compared with normal BMI, was associated with improved survival in patients with metastatic melanoma (average adjusted hazard ratio [HR] 0·77 [95% CI 0·66-0·90] for progression-free survival and 0·74 [0·58-0·95] for overall survival). The survival benefit associated with obesity was restricted to patients treated with targeted therapy (HR 0·72 [0·57-0·91] for progression-free survival and 0·60 [0·45-0·79] for overall survival) and immunotherapy (HR 0·75 [0·56-1·00] and 0·64 [0·47-0·86]). No associations were observed with chemotherapy (HR 0·87 [0·65-1·17, pinteraction=0·61] for progression-free survival and 1·03 [0·80-1·34, pinteraction=0·01] for overall survival). The association of BMI with overall survival for patients treated with targeted and immune therapies differed by sex, with inverse associations in men (HR 0·53 [0·40-0·70]), but no associations observed in women (HR 0·85 [0·61-1·18, pinteraction=0·03]). INTERPRETATION: Our results suggest that in patients with metastatic melanoma, obesity is associated with improved progression-free survival and overall survival compared with those outcomes in patients with normal BMI, and that this association is mainly seen in male patients treated with targeted or immune therapy. These results have implications for the design of future clinical trials for patients with metastatic melanoma and the magnitude of the benefit found supports further investigation of the underlying mechanism of these associations. FUNDING: ASCO/CCF Young Investigator Award, ASCO/CCF Career Development Award, MD Anderson Cancer Center (MDACC) Melanoma Moonshot Program, MDACC Melanoma SPORE, and the Dr Miriam and Sheldon G Adelson Medical Research Foundation.

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis.

BACKGROUND: Despite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune-related adverse events (irAEs), including neurologic events ranging from mild headache to potentially life-threatening encephalitis. Here, we summarize neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment, present cases of treatment-related encephalitis, and provide practical guidance on diagnosis and management. METHODS: We searched a Global Pharmacovigilance and Epidemiology database for neurologic irAEs reported over an 8-year period in patients with advanced melanoma receiving nivolumab with or without ipilimumab from 12 studies sponsored by Bristol-Myers Squibb. Serious neurologic irAEs were reviewed, and relationship to nivolumab or ipilimumab was assigned. RESULTS: In our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious neurologic irAEs, including neuropathy (n = 22), noninfective meningitis (n = 5), encephalitis (n = 6), neuromuscular disorders (n = 3), and nonspecific adverse events (n = 7). Study drug was discontinued (n = 20), interrupted (n = 8), or unchanged (n = 7). Most neurologic irAEs resolved (26/35 patients; 75%). Overall, median time to onset was 45 days (range 1-170) and to resolution was 32 days (2-809+). Median time to onset of encephalitis was 55.5 days (range 18-297); four cases resolved and one was fatal. CONCLUSION: Both oncologists and neurologists need to be aware of signs and symptoms of serious but uncommon neurologic irAEs associated with checkpoint inhibitors. Prompt diagnosis and management using an established algorithm are critical to minimize serious complications from these neurologic irAEs. IMPLICATIONS FOR PRACTICE: With increasing use of checkpoint inhibitors in cancer, practicing oncologists need to be aware of the potential risk of neurologic immune-related adverse events and be able to provide prompt treatment of this uncommon, but potentially serious, class of adverse events. We summarize neurologic adverse events related to nivolumab alone or in combination with ipilimumab in patients with advanced melanoma from 12 studies and examine in depth 6 cases of encephalitis. We also provide input and guidance on the existing neurologic adverse events management algorithm for nivolumab and ipilimumab.

Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma.

PURPOSE: CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. METHODS: CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. RESULTS: Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. CONCLUSION: The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736.

Exceptional response and multisystem autoimmune-like toxicities associated with the same T cell clone in a patient with uveal melanoma treated with immune checkpoint inhibitors.

Balancing the potential for durable remissions with autoimmune-like toxicities is a key clinical challenge in the use of immune checkpoint inhibitors (ICI). Certain toxicities are associated with an increased response rate; however, the molecular underpinnings of this association are poorly understood. Here, we report a patient with wide spread uveal melanoma who had an exceptional response to treatment with ipilimumab and nivolumab, but suffered severe immune-related sequelae, including central serous retinopathy with retinal detachment, tinnitus, and vitiligo resembling Vogt-Koyanagi-Harada disease, and refractory enteritis. TCR-sequencing of the primary tumor, a hepatic metastasis, duodenal biopsy and peripheral blood mononuclear cells, identified the identical T cell clone in all four tissues. This case provides preliminary evidence for cross-reactivity as a mechanism for the association between effect and toxicity of ICIs.

Association of Autoimmune Encephalitis With Combined Immune Checkpoint Inhibitor Treatment for Metastatic Cancer.

IMPORTANCE: Paraneoplastic encephalitides usually precede a diagnosis of cancer and are often refractory to immunosuppressive therapy. Conversely, autoimmune encephalitides are reversible conditions that can occur in the presence or absence of cancer. OBJECTIVE: To report the induction of autoimmune encephalitis in 2 patients after treatment of metastatic cancer with a combination of the immune checkpoint inhibitors nivolumab and ipilimumab. DESIGN, SETTING, AND PARTICIPANTS: A retrospective case study was conducted of the clinical and management course of 2 patients with progressive, treatment-refractory metastatic cancer who were treated with a single dose each (concomitantly) of the immune checkpoint inhibitors nivolumab, 1 mg/kg, and ipilimumab, 3 mg/kg. EXPOSURES: Nivolumab and ipilimumab. MAIN OUTCOMES AND MEASURES: The clinical response to immunosuppressive therapy in suspected autoimmune encephalitis in the setting of immune checkpoint inhibitor use. RESULTS: Autoantibody testing confirmed identification of anti-N-methyl-D-aspartate receptor antibodies in the cerebrospinal fluid of 1 patient. Withdrawal of immune checkpoint inhibitors and initiation of immunosuppressive therapy, consisting of intravenous methylprednisolone sodium succinate equivalent to 1000 mg of methylprednisolone for 5 days, 0.4 mg/kg/d of intravenous immunoglobulin for 5 days, and 2 doses of rituximab, 1000 mg, in 1 patient and oral prednisone, 60 mg/d, in the other patient, resulted in improved neurologic symptoms. CONCLUSIONS AND RELEVANCE: Immune checkpoint inhibition may favor the development of immune responses against neuronal antigens, leading to autoimmune encephalitis. Early recognition and treatment of autoimmune encephalitis in patients receiving immune checkpoint blockade therapy will likely be essential for maximizing clinical recovery and minimizing the effect of drug-related toxic effects. The mechanisms by which immune checkpoint inhibition may contribute to autoimmune encephalitis require further study.

Encontros e Desencontros entre o Pensamento de Husserl e Heidegger: Fenomenologia em Movimento / Encounters and Mismatches between Husserl and Heidegger's Thought: Phenomenology in Motion / Encuentros y desajustes entre el pensamiento de Husserl y Heidegger: Fenomenología en movimiento

O artigo em questão busca discorrer sobre a relevância da fenomenologia de Edmund Husserl no pensamento de Martin Heidegger, em especial em sua obra Ser e tempo de 1927. Mostraremos como as ideias absolutamente paradigmáticas de Husserl se opõem a todo um modo de pensar hegemônico que permanece até os dias de hoje, destacando a noção de intencionalidade que não foi superada ou descartada por Heidegger, mas radicalizada em suas reflexões sobre o existente humano e sua estrutura ontológica originária. De forma a contribuir para o desenvolvimento da compreensão da relação do pensamento desses dois filósofos, ressaltamos que o eixo central deste trabalho consiste em descrever o método fenomenológico husserliano e sua apropriação peculiar no pensamento heideggeriano sobre o existir humano e seu projeto em Ser e tempo, a fim de demonstrar como a fenomenologia de Husserl constituiu pedra angular e imprescindível para a analítica existencial presente em Ser e tempo, sem com isso deixar de apontar algumas diferenças entre os dois pensadores. (AU)

The article in question seeks to discuss the relevance of Edmund Husserl's phenomenology in Martin Heidegger's thinking, especially in his work Being and Time of 1927. We will show how Husserl's absolutely paradigmatic ideas are opposed to a whole hegemonic way of thinking until today, highlighting the notion of intentionality that was not overcome or discarded by Heidegger, but radicalized in his reflections on the existing human and its original ontological structure. In order to contribute to the development of the understanding of the thought relationship of these two philosophers, we emphasize that the central axis of this work consists of describing the Husserlian phenomenological method and its peculiar appropriation in Heidegger's thought about human existence and its project in Being and time, in order to demonstrate how Husserl's phenomenology constituted a cornerstone and essential for the existential analytics present in Being and Time, without failing to point out some differences between the two thinkers. (AU)

El artículo en cuestión busca discutir la relevancia de la fenomenología de Edmund Husserl en el pensamiento de Martin Heidegger, especialmente en su obra Ser y tiempo de 1927. Mostraremos cómo las ideas absolutamente paradigmáticas de Husserl se oponen a una forma de pensamiento hegemónica completa hasta hoy, destacando la noción de intencionalidad que no fue superada ni descartada por Heidegger, sino que se radicalizó en sus reflexiones sobre el ser humano existente y su estructura ontológica original. Para contribuir al desarrollo de la comprensión de la relación de pensamiento de estos dos filósofos, enfatizamos que el eje central de este trabajo consiste en describir el método fenomenológico husserliano y su apropiación peculiar en el pensamiento de Heidegger sobre la existencia humana y su proyecto en Ser y tiempo, para demostrar cómo la fenomenología de Husserl constituyó una piedra angular e indispensable para la analítica existencial presente en el Ser y el Tiempo, sin dejar de señalar algunas diferencias entre los dos pensadores. (AU)

Germline CDKN2A mutations in Brazilian patients of hereditary cutaneous melanoma.

Approximately 10 % of all cutaneous melanoma cases occur in a familial context. The major susceptibility gene for familial melanoma is CDKN2A. In Latin America, genetic studies investigating melanoma predisposition are scarce. The aim of this work was to investigate germline CDKN2A point mutations and genomic rearrangements in a cohort of 59 Brazilian melanoma-prone patients. Screening of CDKN2A alterations was performed by sequencing and multiplex ligation probe amplification. Germline CDKN2A mutations affecting p16(INK4a) were detected in 8 unrelated probands (13.6 %), including 7 familial cases and one patient with multiple melanomas; 4 out of 8 mutation carriers met the criteria for familial melanoma and had multiple primary lesions. Although this study adds to the literature on melanoma susceptibility in Latin America, it is limited by the small size of the cohort. Our findings suggest that stringent inclusion criteria led to a substantially increased rate of CDKN2A mutation detection. This consideration should be taken into account when referring patients for genetic screening in a setting of limited budget, such as in developing countries.

Atypical mole syndrome and dysplastic nevi: identification of populations at risk for developing melanoma - review article.

Atypical Mole Syndrome is the most important phenotypic risk factor for developing cutaneous melanoma, a malignancy that accounts for about 80% of deaths from skin cancer. Because the diagnosis of melanoma at an early stage is of great prognostic relevance, the identification of Atypical Mole Syndrome carriers is essential, as well as the creation of recommended preventative measures that must be taken by these patients.

Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma

PURPOSE:CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America.METHODS:CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained.RESULTS:Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients.CONCLUSION:The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives(AU)

Atypical mole syndrome and dysplastic nevi: identification of populations at risk for developing melanoma: review article

Atypical Mole Syndrome is the most important phenotypic risk factor for developing cutaneous melanoma, a malignancy that accounts for about 80 percent of deaths from skin cancer. Because the diagnosis of melanoma at an early stage is of great prognostic relevance, the identification of Atypical Mole Syndrome carriers is essential, as well as the creation of recommended preventative measures that must be taken by these patients.

Caracterização do lócus CDKN2A e dos genes CDK4 e MC1R em pacientes com critérios clínicos para o diagnóstico da síndrome do melanoma familial e melanoma múltiplo esporádico / Caracterization of the CDKN2A, CDK4 and MC1R genes in patients with clinical criteria for the diagnosis of Familial Melanoma Syndrome and Multiple Sporadic Melanoma

A Síndrome do Melanoma Familial (SMF) é uma síndrome rara de predisposição ao câncer associada preponderantemente ao lócus CDKN2A. Algumas poucas famílias no mundo apresentam mutações no gene CDK4, relacionado a mesma via molecular da pRb. Fatores relacionados ao fenótipo e polimorfismos do gene MC1R modulam de desenvolvimento de melanoma nestes pacientes. Os objetivos deste trabalho são pesquisar as mutações germinativas do lócus CDKN2A e do gene CDK4, além de caracterizar os polimorfismos dos gene MC1R em famílias brasileiras com diagnóstico clínico de Síndrome do Melanoma Familial (SMF) e em pacientes com Melanoma Múltiplo Esporádico (MME) e descrever os fatores de risco pessoais e ambientais de melanoma em probandos e familiares. Foram incluídos 50 probandos que preencheram os critérios clínicos, sendo 32 para SMF e 18 para MME. A metodologia incluiu o seqüenciamento direto dos 4 éxons do lócus CDKN2A, do éxon 2 do gene CDK4 e do éxon único do gene MC1R. Foram encontradas 8 mutações germinativas e uma alteração no lócus CDKN2A. Nenhuma mutação foi detectada no gene CDK4. Uma ampla variedade de polimorfismos do MC1R foi encontrada em 87% dos pacientes pesquisados. As mutações patogênicas p.Pro48Thr e c.-34G>T foram as mais freqüentes, sendo detectadas em 3 probandos cada uma. Cada um dos demais probandos apresentaram as mutações p.Gly101Trp e c.IVS-105A>G. A alteração p.Val84Met nunca descrita na literatura foi detectada em um dos probandos e tem potencial patogênico incerto. Estudos adicionais de segregação e funcionais são necessários. Este estudo é o quarto estudo realizado na América Latina a respeito da definição das mutações dos genes de predisposição ao Melanoma Familial e Melanoma Múltiplo Esporádico, sendo o único com critérios de seleção que seguem o padrão dos outros estudos descritos na literatura.

A Pós-Graduação da Faculdade de Medicina da UFMG: Avaliação do Programa Teórico pelos Egressos / Graduate Studies at the UFMG School of Medicine: Na Evaluation of the Theoretical Course Load by Alumni

Resumo: Esta pesquisa foi delineada para buscar informações complementares ao processo de avaliação dos cursos de pós-graduação da Faculdade de Medicina da Universidade de Minas Gerais. Questionários foram elaborados e encaminhados aos 399 egressos do período 1979-95. Um dos objetivos foi avaliar as disciplinas consideradas básicas para a formação pedagógica e de instrumentação em metodologia de pesquisa: Didática Médica, Epidemiologia Humana, Bioestatística, Metodologia Científica e Normalização Bibliográfica. A população que responderam os questionários foi de 260 (65,8%). Cerca de 60% dos egressos avaliaram as disciplinas com o conteúdo "adequado", carga horária "suficiente", didática entre "ótima e boa", recursos audiovisuais entre "excelentes e satisfatórios" e aproveitamento "suficiente". Os dados remetam a uma reavaliação das disciplinas.

Abstract: This research aimed at gathering supplementary information for the evaluation process focusing on graduate courses at the School of Medicine of the federal University in Minas Gerais. Questionnaires were prepared and submitted to the 399 alumni from the period 1979-95. One of the objectives was to evaluate what are considered basic courses for training in teaching and research methodology: Medical Teaching, Human Epidelilogy, Biostatistics, Scientific Methodology, and Bibliographical Standarzation. A total of 260 alumni (65.8%) answered the questionnaire, 60% of whom evaluate the courses as having "adequate" content, "sufficient" course hours, didactics ranging from "fine" to "good", audiovisual resources ranging from "excellent" to "satisfactory" and "sufficient" yield. The data suggest the need for a review of the courses.

Descriçäo de algumas características da populaçäo infantil em duas comunidades da cidade de Pelotas, RS / Epidemiologic inquiry about health conditions among children in two districs of the city of Pelotas, RS

Este trabalho foi um inquérito epidemiológico sobre as condiçöes de saúde infantil realizado em duas comunidades, Vila Real e Vila Farroupilha, situadas na cidade de Pelotas, RS, com o intuito de subsidiar as atividades desenvolvidas no Posto de Saúde Local. Nas crianças até 3 anos de idade foram coletadas informaçöes sobre gênero, idade, utilizaçäo de serviços de saúde (motivos e locais), peso ao nascer, percentual de crianças que frequentaram programas de puericultura, cobertura vacinal, duraçäo de amamentaçäo natural e se as mäes das crianças haviam feito prée-natal. Os questionários foram respondidos pelas próprias mäes. Entre as 149 crianças encontradas, verificou-se que a média mensal de consultas era de 1,3, estimando-se em 15,6 por ano, sendo que principal motivo de consultas foram Puericultura e Infecçöes das Vias Aéreas Superiores. Entre as crianças menores de um ano, 96 por cento estavam inscritas em Programas de Puericultura. Encontrou-se 10 por cento de crianças com baixo peso ao nascimento, Constatou-se que, embora 90 por cento das crianças iniciassem o aleitamento materno, 59 por cento era amamentada por menos de 6 meses. A cobertura vacinal foi de 89,2 por cento para BCG, 75,2 por cento para as vacinas antipoliomielite e DPT e 71,8 por cento para anti-sarampo. Este tipo de inquérito é rápido, barato, fácil de realizar e pode contribuir de forma objetiva para o aperfeiçoamento das açöes de saúde

Uso de las guías de práctica clínica por los médicos de un hospital general / Use of clinical practice guidelines by physicians in a general hospital

Objetivos: Conocer el porcentaje de médicos que utiliza las guías de práctica clínica en nuestro centro, sus motivos, el tipo de guías que emplean, su opinión sobre ellas y cómo las evalúan. Material y métodos: Se encuestó a 161 médicos de 32 especialidades clínicas. El cuestionario tenía 17 preguntas cerradas y una abierta, referidas al uso de las guías de práctica clínica. Resultados: Respondieron 78 médicos (48,4 por ciento) de 30 especialidades. De ellos, 38 (48,7 por ciento) contestaron que nunca o pocas veces utilizan las guías de práctica clínica, 61 (78,2 por ciento) consideran que las guías disminuyen la variabilidad, 64 (82 por ciento) que mejoran la calidad asistencial, 31 (39,7 por ciento) que están influenciadas por la industria farmacéutica, y 60 (76,9 por ciento) que es útil elaborar guías propias. De los 40 (51,3 por ciento) médicos que utilizan las guías, 35 (87,5 por ciento) las emplean para mejorar la asistencia, 21 (52,5 por ciento) usan las de las sociedades científicas, 5 (12,5 por ciento) las propias, y 14 (35 por ciento), ambas. En la mayoría de los servicios las guías rara vez se evalúan o bien se valoran mediante opiniones individuales. Conclusiones: Un porcentaje significativo de nuestros clínicos no utiliza habitualmente las guías de práctica clínica, a pesar de que la mayoría las considera útiles. Los que las suelen utilizar lo hacen para mejorar la calidad asistencial y emplean habitualmente las de las sociedades científicas. Un 40 por ciento opina que las guías están influenciadas por la industria farmacéutica. La mayoría considera útil elaborar guías propias. Las guías no se suelen utilizar de forma homogénea ni se evalúan convenientemente (AU)