Comportamientos de protección solar y percepción de riesgo de cáncer de piel en la población española

Tesis descargada de TESEOntroducción: La exposición solar constituye un factor de riesgo modificable para los tumores de piel. El cambio en los hábitos de la población ha llevado a un aumento en la incidencia de tumores cutáneos y a su aumento en las últimas décadas. Los tumores cutáneos no melanoma, si bien se excluyen normalmente de los registros de cáncer, constituyen un problema de salud pública y el melanoma constituye un tumor con mortalidad elevada y tasas de supervivencia de solo 5% a los 5 años de seguimiento en el que la exposición solar es un factor de riesgo conocido. El uso de cremas con FPS, así como otros elementos de protección son reconocidos medios para evitar los daños de la exposición, y por tanto, actuar como factores preventivos del daño cutáneo. El conocimiento del factor de riesgo modificable para el desarrollo de tumores cutáneos hace insistir en su conocimiento, nivel de concienciación del peligro de la exposición y hábitos relacionados con el mismo, como posibles elementos modificadores del desarrollo de la enfermedad. Material y método: estudio transversal, descriptivo de corte poblacional realizado mediante encuesta estructurada a una muestra representativa de la población española en sexo, edad y distribución por localización urbana o rural y por área geográfica (n=1100). Objetivos: Primario: Conocer los hábitos de exposición al sol en la población española: obtener información sobre las diferentes situaciones, lugares y duración/intensidad de la exposición a la radiación solar, segmentada por edad, sexo, área geográfica y hábitat. Secundarios: Conocer las pautas de comportamiento de protección frente al sol: conocer los diferentes tipos de protección al sol utilizados por la población española, uso de cremas solares (factor de protección solar y frecuencia de aplicación) y cuidado de protección a los hijos. Conocer los niveles de percepción de riesgo de la radiación solar asociado a la exposición al sol en las diferentes etapas de la vida, así como sus consecuencias, y también el grado de concienciación respecto al melanoma. Obtener información respecto a la percepción de riesgo asociado a las cabinas/lámparas solares. Conclusiones: El conocimiento de los hábitos de exposición en la población española, así como de la conciencia del nivel de exposición y el uso adecuado de los factores conocidos de protección ante la exposición solar en diferentes situaciones (vida diaria, vacaciones, trabajo, cuidado de los hijos) y la conciencia del nivel de riesgo relacionada con estos hábitos, nos permitirá seleccionar una población susceptible de mejora en las campañas informativas al respecto que pueden influir en mejores resultados preventivos en este área

Safety and efficacy of colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia as part of a macro-project funded by the Seventh Framework Program of the European Commission studying off-patent antibiotics. study protocol for a randomized controlled trial

Background: Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrugresistant gram-negative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, is now the antimicrobial with greatest in vitro activity against MDR-GNB. Methods/Design: The MagicBullet clinical trial is an investigator-driven clinical study, funded by the Seventh Framework Program of the European Commission. This is designed as a phase IV, randomized, controlled, open label, non-inferiority and international trial to assess the safety and efficacy of colistin versus meropenem in late onset VAP. The study is conducted in a total of 32 centers in three European countries (Spain, Italy and Greece) with specific high incidences of infections caused by MDR-GNB. Patients older than 18 years who develop VAP with both clinical and radiological signs, and are on mechanical ventilation for more than 96 hours, or less than 96 hours but with previous antibiotic treatment plus one week of hospitalization, are candidates for inclusion in the study. A total sample size of 496 patients will be randomized according to a severity clinical score (at the time of VAP diagnosis in a 1:1 ratio to receive either colistin 4.5 MU as a loading dose, followed by 3 MU every eight hours (experimental arm), or meropenem 2 g every eight hours (control arm), both combined with levofloxacin. Mortality from any cause at 28 days will be considered as the main outcome. Clinical and microbiological cure will be evaluated at 72 hours, eight days, the finalization of antibiotic treatment, and 28 days of follow-up. The efficacy evaluation will be performed in every patient who receives at least one study treatment drug, and with etiologic diagnosis of VAP, intention-to-treat population and per protocol analysis will be performed

Identification of a novel human E-Cadherin splice variant andassessment of its effects upon EMT-related events

Epithelial Cadherin (E-cadherin) is involved in calcium-dependent cell-cell adhesion and signal transduction. The E-cadherin decrease/loss is a hallmark of Epithelial to Mesenchymal Transition (EMT), a key event in tumor progression. The underlying molecular mechanisms that trigger E-cadherin loss and consequent EMT have not been completely elucidated. This study reports the identification of a novel human E-cadherin variant mRNA produced by alternative splicing. A bioinformatics evaluation of the novel mRNA sequence and biochemical verifications suggest its regulation by Nonsense-Mediated mRNA Decay (NMD). The novel E-cadherin variant was detected in 29/42 (69%) human tumor cell lines, expressed at variable levels (E-cadherin variant expression relative to the wild type mRNA = 0.05-11.6%). Stable transfection of the novel E-cadherin variant in MCF-7 cells (MCF7Ecadvar) resulted in downregulation of wild type E-cadherin expression (transcript/protein) and EMT-related changes, among them acquisition of a fibroblastic-like cell phenotype, increased expression of Twist, Snail, Zeb1, and Slug transcriptional repressors and decreased expression of ESRP1 and ESRP2 RNA binding proteins. Moreover, loss of cytokeratins and gain of vimentin, N-cadherin and Dysadherin/FXYD5 proteins was observed. Dramatic changes in cell behavior were found in MCF7Ecadvar, as judged by the decreased cell-cell adhesion (Hanging-drop assay), increased cell motility (Wound Healing) and increased cell migration (Transwell) and invasion (Transwell w/Matrigel). Some changes were found in MCF-7 cells incubated with culture medium supplemented with conditioned medium from HEK-293 cells transfected with the E-cadherin variant mRNA. Further characterization of the novel E-cadherin variant will help understanding the molecular basis of tumor progression and improve cancer diagnosis.Fil: Matos, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lapyckyj, Lara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rosso, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Besso, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Mencucci, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Marin Briggiler, Clara Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Giustina, Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Furlong, Laura Ines. Universitat Pompeu Fabra; EspañaFil: Vazquez, Monica Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Opportunities for antibiotic optimisation and outcome improvement in patients with negative blood cultures: study protocol for a cluster-­randomised crossover trial, the NO-­BACT study.

Introduction Patients with negative blood cultures (BCx) represent 85%–90% of all patients with BCx taken during hospital admission. This population usually includes a heterogeneous group of patients admitted with infectious diseases or febrile syndromes that require a blood culture. There is very little evidence of the clinical characteristics and antibiotic treatment given to these patients. Methods and analysis In a preliminary exploratory prospective cohort study of patients with BCx taken, the clinical/therapeutic characteristics and outcomes/ antimicrobial stewardship opportunities of a population of patients with negative BCx will be analysed. In the second phase, using a cluster randomised crossover design, the implementation of an antimicrobial stewardship intervention targeting patients with negative BCx will be evaluated in terms of quality of antimicrobial use (duration and de-escalation), length of hospital stay and mortality. Ethics and dissemination This study has been and registered with clinicaltrials.gov. The findings of our study may support the implementation in clinical practice of an antimicrobial stewardship intervention to optimise the use of antibiotics in patients with negative BCx. The results of this study will be published in peer-reviewed journals and disseminated at national and international conferences. Trial registration number NCT03535324.Instituto de Salud Carlos III PI17 / 01809Plataforma Española de Investigación Clínica y Ensayos Clínicos, SCReN (Red Española de Investigación Clínica), financiada por la Subdirección General de Evaluación y Promoción de la Investigación ISCIII: PT17 / 0017/0012. Cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER)

Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial.

Background: Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined. Methods: A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7–14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved. Results: A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of − 2.16 (− 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015). Conclusions: This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination.Seventh Framework Program of the European Commission. Magic Bullet: 278232

Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial

Introduction Finding therapeutic alternatives to carbapenems in infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future. Methods and analysis The main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a ‘real practice’ multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli. Ethics and dissemination Ethical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals. Discussion This project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects with this drug, whether as monotherapy or combination therapy

Targeted Simplification Versus Antipseudomonal Broad-Spectrum Beta-Lactams in Patients With Bloodstream Infections Due to Enterobacteriaceae (SIMPLIFY): A Study Protocol for a Multicentre, Open-Label, Phase III Randomised, Controlled, Non-Inferiority Clinical Trial.

Introduction Within the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare- associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable. Methods and analysis The SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic ‘real-practice’ trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due to Enterobacteriaceae. The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals. Ethics and dissemination Each participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals. [Discussion] Strategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation.Instituto de Salud Carlos III (ISCIII): PI15/00439, integrado en el Plan Nacional de I+D+i 2013-2016 y cofinanciado por la Unión Europea (ERDF/ESF, “Investing in your future”)

Bases moleculares da interação celular em modelos de reprodução e câncer: identificação de proteínas e mecanismos envolvidos

La interacción entre las células somáticas y entre las gametas involucra una serie de eventos moleculares que no han sido dilucidados totalmente. Nuestro grupo de investigación ha desarrollado proyectos dirigidos a profundizar el conocimiento de dichos eventos. Los estudios han comprendido el análisis de moduladores de la funcionalidad espermática (ej. efecto de la temperatura de incubación, las concentraciones del ión calcio, los anticuerpos antiespermáticos de fluidos biológicos en la motilidad, la capacitación y la exocitosis acrosomal). Asimismo, hemos caracterizado componentes del espermatozoide (ej. CaM Kinasa IV, proacrosina/acrosina) y de secreciones del tracto femenino (ej. Grp78/BiP), evaluado su rol en el desarrollo de capacidad fecundante y, en algunos casos, investigado su relación con la infertilidad. En años recientes, nuestros proyectos se han extendido al estudio de las cadherinas en eventos de adhesión celular durante la fecundación; hemos caracterizado la expresión de cadherina epitelial y neural en tejidos reproductivos y gametas y evaluado su participación en la fecundación. Dada su reconocida relevancia en el cáncer, hemos abordado estudios en diversos modelos tumorales. Nuestras investigaciones han contribuido a la comprensión de los eventos de interacción de las gametas durante la fecundación así como entre las células somáticas durante la progresión tumoral.Cell-cell interaction between somatic cells as well as gametes involves molecular events that have not been completely elucidated. Our research group has developed projects aimed at studying proteins and mechanisms participating in these interactions. Several modulators of sperm functions have been analyzed (i.e. incubation temperature, calcium ion concentration, and antisperm antibodies present in biological fluids upon sperm motility, capacitation and acrosomal exocytosis). In addition, proteins from spermatozoa (i.e. CaM Kinase IV, proacrosin/acrosin) and from secretions of the female tract (Grp78/BiP) have been characterized, and their role in the development of sperm fertilizing ability assessed. In some cases, their relationship with infertility was evaluated. In recent years, our projects have been extended to study members of the cadherin superfamily and related proteins; in particular, the expression of epithelial and neural cadherin in reproductive tissues and gametes was characterized and evidence of their participation in fertilization-related cell-cell adhesion events shown. Based on the vast evidence of the role of these proteins in tumor progression, our current research also involves studies of cancer models. Our projects have contributed to the understanding of the molecular basis of cell-cell interaction during fertilization as well as during tumor progression.A interação entre as células somáticas e entre os gametas envolve uma série de eventos moleculares que não têm sido elucidados totalmente. Nosso grupo de pesquisa tem desenvolvido projetos encaminhados a aprofundar o conhecimento de tais eventos. Os estudos têm compreendido a análise de moduladores da funcionalidade espermática (ex. efeito da temperatura de incubação, as concentrações do íon cálcio, os anticorpos antiespermáticos de fluidos biológicos na motilidade, a capacitação e a exocitose acrossomal). Do mesmo modo, caracterizamos componentes do espermatozoide (ex. CaM Kinase IV, proacrosina /acrosina) e de secreções do trato feminino (ex. Grp78/BiP), avaliamos seu papel no desenvolvimento de capacidade fecundante e, em alguns casos, investigamos sua relação com a infertilidade. Em anos recentes, nossos projetos se têm estendido ao estudo das caderinas em eventos de adesão celular durante a fecundação; temos caracterizado a expressão de caderina epitelial e neural em tecidos reprodutivos e gametas e avaliamos sua participação na fecundação. Dada sua reconhecida relevância no câncer, temos abordado estudos em diversos modelos tumorais. Nossas pesquisas têm contribuído à compreensão dos eventos de interação dos gametas durante a fecundação bem como entre as células somáticas durante a progressão tumoralFil: Vazquez, Monica Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Furlong, Laura I.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Marin Briggiler, Clara Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Veaute, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Veiga, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Matos, María L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Lapyckyj, Lara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Gabrielli, Nieves María. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Rosso, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Arzondo, María M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Edelsztein, Nadia Yasmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Besso, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin