Tumor budding in upper gastrointestinal carcinomas.

The basis of personalized medicine in oncology is the prediction of an individual's risk of relapse and death from disease. The presence of tumor budding (TB) at the tumor-host interface of gastrointestinal cancers has been recognized as a hallmark of unfavorable disease biology. TB is defined as the presence of dedifferentiated cells or small clusters of up to five cells at the tumor invasive front and can be observed in aggressive carcinomas of the esophagus, stomach, pancreas, ampulla, colon, and rectum. Presence of TB reproducibly correlates with advanced tumor stage, frequent lymphovascular invasion, nodal, and distant metastasis. The UICC has officially recognized TB as additional independent prognostic factor in cancers of the colon and rectum. Recent studies have also characterized TB as a promising prognostic indicator for clinical management of esophageal squamous cell carcinoma, adenocarcinoma of the gastro-esophageal junction, and gastric adenocarcinoma. However, several important issues have to be addressed for application in daily diagnostic practice: (1) validation of prognostic scoring systems for TB in large, multi-center studies, (2) consensus on the optimal assessment method, and (3) inter-observer reproducibility. This review provides a comprehensive analysis of TB in cancers of the upper gastrointestinal tract including critical appraisal of perspectives for further study.

Current status and recommendations for use of the frozen elephant trunk technique: a position paper by the Vascular Domain of EACTS.

The implementation of new surgical techniques offers chances but carries risks. Usually, several years pass before a critical appraisal and a balanced opinion of a new treatment method are available and rely on the evidence from the literature and expert's opinion. The frozen elephant trunk (FET) technique has been increasingly used to treat complex pathologies of the aortic arch and the descending aorta, but there still is an ongoing discussion within the surgical community about the optimal indications. This paper represents a common effort of the Vascular Domain of EACTS together with several surgeons with particular expertise in aortic surgery, and summarizes the current knowledge and the state of the art about the FET technique. The majority of the information about the FET technique has been extracted from 97 focused publications already available in the PubMed database (cohort studies, case reports, reviews, small series, meta-analyses and best evidence topics) published in English.

Invariantes del pensamiento en los arquitectos de Madrid. Primera década del siglo XXI. Una historia de transmisión oral

Invariantes del pensamiento en los arquitectos de Madrid. Primera década del siglo XXI. Una historia de transmisión oral es una Tesis Doctoral que parte de la elaboración de un archivo documental inédito, archivo que aglutina los testimonios de los más importantes arquitectos de Madrid presentes durante los primeros diez años del siglo XXI. Estos testimonios se recogen ordenadamente a modo de conversaciones transcritas, reflexiones puntuales y audios. La incorporación de los audios al trabajo documental permite comprobar a futuros investigadores, de manera directa, la certeza de las conclusiones o, incluso, establecer interpretaciones distintas. Los documentos sonoros son el germen de este trabajo. La Tesis Doctoral ordena e interpreta los testimonios en su apartado de ANÁLISIS/ DESARROLLO permitiendo entender a través de constantes demostraciones un hilo conductor del pensamiento en los arquitectos de Madrid. Se trata de una Tesis Doctoral que se entiende como un documento vivo, abierto y que gracias a su carácter inédito descubre matices y reflexiones de los arquitectos nunca antes recogidos en otros trabajos. Se ha conseguido reunir y ordenar por primera vez la voz y el pensamiento de los más importantes arquitectos de Madrid, muchos de ellos ya fallecidos. Se ha establecido un árbol genealógico ordenado y completo de los arquitectos de referencia indiscutibles desde el año 1939. Se ha conseguido reunir en un solo documento a los arquitectos y personajes más citados y recurrentes en el discurso de los arquitectos de Madrid, pudiendo constatar así sus referentes culturales más utilizados. Se ha descubierto y argumentado un pensamiento común dividido en cuatro conceptos: Oportunidad, Orden, Compromiso y Contención. Se produce una aproximación al arquitecto y a su pensamiento de la manera más natural y espontánea. Las grabaciones nos permitirán introducirnos, sin imposturas, no solo en el fondo, sino también en la forma de lo que se comunica, en el cómo. Una vez seleccionados los documentos sonoros más adecuados para el objetivo de este trabajo se ha procedido a su transcripción al papel. En este proceso se depura el lenguaje y se liman defectos de forma, al mismo tiempo se resumen las conversaciones y se recogen solo los comentarios más interesantes. En el proceso de transcripción, así como en la elección de las preguntas, existe una labor editorial, la aplicación de un criterio a la hora de seleccionar, resumir, corregir, completar, etc. Para abordar las conversaciones se ha recurrido a la bibliografía de referencia de cada uno de los arquitectos. Una vez transcritas las entrevistas, se establece una valoración crítica, una aproximación teórica al tema principal de la conversación. Bien puede tratarse de una reflexión sobre el arquitecto y su trabajo o sobre algunas de las opiniones o temas vertidos durante la charla. Para situar a cada uno de los arquitectos que se citan, se ha establecido un apartado genealógico completo donde cada uno se coloca en su lugar correspondiente conforme a sus apariciones en los textos principales de la historiografía reciente desde Carlos Flores hasta el año 2010. Esta Tesis Doctoral es un testigo de la diversidad de pensamientos y actitudes así como de las coincidencias. Las conversaciones mantenidas, las reflexiones y las opiniones vertidas al respecto han tocado reiteradamente muchos temas que aparecerán ordenados en el ANÁLISIS/DESARROLLO y en el apartado DESCRIPTORES. A partir de estos y otros temas genéricos, los pensamientos se aglutinan en torno a cuatro puntos que resumen las actitudes y los planteamientos conceptuales más recurrentes y coincidentes. Estos cuatro puntos definen de una manera concreta al arquitecto de Madrid. Oportunidad, Orden, Compromiso y Contención. Identidad generada a través de una historia de transmisión oral, desde los arquitectos de las primeras generaciones de posguerra hasta hoy. ABSTRACT Invariable thought in the architects of Madrid. First decade of the XXI century. A history of oral transmission is a Doctoral Thesis that starts with the development of a new documentary file, a file which brings together the testimonies of the most important architects of Madrid present during the first ten years of this century. These testimonies include conversations, punctual reflections and audio bites. Incorporating audio allows future researchers to check certain conclusions directly or even to have different interpretations. Sound bites are the seed of this work. This Doctoral Thesis orders and interprets the testimonies in the ANALYSIS / DEVELOPMENT section, through which a common thread of thought in Madrid architects can be ascertained. This doctoral thesis is meant as a living, open document, which, thanks to its unprecedented nature, discovers nuances and reflections of architects that had never been collected in previous studies. It has brought together and sorted for the first time the voice and thoughts of the most important architects of Madrid, many of them already deceased. It has established an orderly and comprehensive reference guide to the most important architects since 1939. It has brought together in one document the most cited and recurring architects and characters in the discourse of the architects of Madrid, which enables us to observe the cultural references they used the most. We have discovered and put forward a common thought divided into four concepts: Opportunity, Order, Commitment and Containment. The architect and his thoughts are revealed as naturally and spontaneously as possible. The recordings allow us to ascertain, without impositions, not only the substance but also the form of what is communicated. After selecting the most appropriate sound bites for the purpose of this work, we have proceeded to transcribe them to paper. In this process the language has been purified and formal defects have been dealt with, and at the same time the conversations have been summarized and only the most interesting comments have been kept. The transcription process and the choice of questions entails editorial work, applying a criterion when selecting, summarizing, amending, supplementing, etc. To address the conversations, the bibliographic reference of each of the architects has been used. Once the interviews have been transcribed, a critical appraisal and a theoretical approach to the main topic of conversation are established. It may be a reflection on the architect and his work or some of the views or issues discussed during the talk. In order to place each of the cited architects, a complete family tree has been devised in which each architect is situated according to his appearances in the main text of recent historiography, from Carlos Flores until 2010. This Doctoral Thesis is a witness to the diversity of thoughts, attitudes and coincidences. The conversations, reflections and opinions expressed in this regard have repeatedly touched many issues that will be sorted in the ANALYSIS/DEVELOPMENT and the KEYWORDS section. From these and other generic issues, thoughts coalesce around four points which summarize the attitudes and the most recurrent and similar conceptual approaches. These four points define the architect of Madrid in a concrete way. Opportunity, order, engagement and containment. An identity generated by a history of oral transmission, from the architects of the first post-war generations until today.

Religion, Democracy and the Public Sphere

Throughout the development and maturation of the American democratic experience, religiously inspired conduct has contributed significantly to democratically progressive political concerns such as the abolition of slavery and campaigns for civil rights, but also the encouragement and perpetuation pf anti-democratic practices such as the institution of slavery and policies of racial segregation. It may be rarely admitted, but there is no essential conceptual affinity between conduct proper to democratic political association. It may, therefore, be useful in our own political circumstances to try to determine boundaries for conduct that expresses and satisfies compatibly both religious and democratic commitments. Perhaps most Americans do recognize – if not in their own cases, at least in reference to the beliefs and actions of others – that religiously inspired conduct is neither thereby justified morally or legally nor absolved from further critical appraisal. Certainly, the history of American legal practice shows that religious belief or inspiration does not serve as acceptable legal defense for conduct charged as criminal infraction. The U.S. Constitution contains only two references to religion: the non-establishment clause prohibits governmental institutionalization of religious beliefs or liberty rights – is limited in scope and application both by other constitutional rights of individuals and by constitutionally authorized powers of government. As the U.S.S.C. has repeatedly held, individual constitutional features must be understood in a manner that harmonizes all stated and implied constitutional features, not by unbridled abstractions of selected phrases. Under the American legal system, there is no absolute or unlimited right to free exercise of religion: not everything done publicly under religious inspiration is legally permissible; what is otherwise illegal conduct is not legalized by religious inspiration. In important respects, general features of the legal boundaries concerning religiously inspired conduct in public life are reasonably clear; nevertheless, broader issues concerning further moral or ethical constraints upon religiously inspired conduct remain unresolved and rarely addressed explicitly.

The place of DPP-4 inhibitors in the treatment algorithm of diabetes type 2 : a systematic review of cost-effectiveness studies

Tese de mestrado, Epidemiologia, Universidade de Lisboa, Faculdade de Medicina, 2015

Can Europe deliver growth? The SAPIR report and beyond. Bruges European Economic Policy (BEEP) Briefing 6/2004

In this critical appraisal of the SAPIR report of July 2003, we choose not to focus on the economic analysis provided in the Sapir Report - where we largely agree - or the analysis of governance questions and design at the EU level. Rather, we concentrate on the assignment, orientation and policy recommendations of the Report with the following question in mind: to what extent does the Report help to revitalize the growth debate in Europe? Unfortunately, the focus of the Report’s recommendations is entirely on the EU level of policy and governance, whereas the motor of growth is very clearly being hindered at the Member State level. The present authors suggest that a number of coordination processes at the EU level are best regarded as ‘dangerous liaisons’which are not really goal-oriented but instead ingeniously seem to serve to protect the actors’ autonomously-decided positions. The Union is trapped in a low-growth equilibrium due to this deceptive construction and because in many policy areas relevant for growth, the EU cannot act without the explicit consent of the Member States, or it simply cannot act at all. Indeed, given the single market and EMU, Europe can only deliver growth at the Member States' level. We exemplify this point in a number of concrete policy areas.

Recommendations for Genetic Testing to Reduce the Incidence of Anthracycline-induced Cardiotoxicity

AIM Anthracycline-induced cardiotoxicity (ACT) occurs in 57% of treated patients and remains an important limitation of anthracycline-based chemotherapy. In various genetic association studies, potential genetic risk markers for ACT have been identified. Therefore, we developed evidence-based clinical practice recommendations for pharmacogenomic testing to further individualize therapy based on ACT risk. METHODS We followed a standard guideline development process; including a systematic literature search, evidence synthesis and critical appraisal, and the development of clinical practice recommendations with an international expert group. RESULTS RARG rs2229774, SLC28A3 rs7853758 and UGT1A6 rs17863783 variants currently have the strongest and the most consistent evidence for association with ACT. Genetic variants in ABCC1, ABCC2, ABCC5, ABCB1, ABCB4, CBR3, RAC2, NCF4, CYBA, GSTP1, CAT, SULT2B1, POR, HAS3, SLC22A7, SCL22A17, HFE and NOS3 have also been associated with ACT, but require additional validation. We recommend pharmacogenomic testing for the RARG rs2229774 (S427L), SLC28A3 rs7853758 (L461L) and UGT1A6*4 rs17863783 (V209V) variants in childhood cancer patients with an indication for doxorubicin or daunorubicin therapy (Level B - moderate). Based on an overall risk stratification, taking into account genetic and clinical risk factors, we recommend a number of management options including increased frequency of echocardiogram monitoring, follow-up, as well as therapeutic options within the current standard of clinical practice. CONCLUSIONS Existing evidence demonstrates that genetic factors have the potential to improve the discrimination between individuals at higher and lower risk of ACT. Genetic testing may therefore support both patient care decisions and evidence development for an improved prevention of ACT.

Appraising the quality of randomized controlled trials: inter-rater reliability for the OTseeker evidence database

Rationale and aims 'OTseeker' is an online database of randomized controlled trials (RCTs) and systematic reviews relevant to occupational therapy. RCTs are critically appraised and rated for quality using the 'PEDro' scale. We aimed to investigate the inter-rater reliability of the PEDro scale before and after revising rating guidelines. Methods In study 1, five raters scored 100 RCTs using the original PEDro scale guidelines. In study 2, two raters scored 40 different RCTs using revised guidelines. All RCTs were randomly selected from the OTseeker database. Reliability was calculated using Kappa and intraclass correlation coefficients [ICC (model 2,1)]. Results Inter-rater reliability was 'good to excellent' in the first study (Kappas >= 0.53; ICCs >= 0.71). After revising the rating guidelines, the reliability levels were equivalent or higher to those previously obtained (Kappas >= 0.53; ICCs >= 0.89), except for the item, 'groups similar at baseline', which still had moderate reliability (Kappa = 0.53). In study 2, two PEDro scale items, which had their definitions revised, 'less than 15% dropout' and 'point measures and variability', showed higher reliability. In both studies, the PEDro items with the lowest reliability were 'groups similar at baseline' (Kappas = 0.53), 'less than 15% dropout' (Kappas

Is modern medicine at risk of losing the plot?

Contemporary medicine has much to its credit, but has created an insatiable demand for new technologies and more health services, fed by commercial promotion, professional advocacy and sociopolitical pressure. Total health expenditure at the national level is now almost 10% of gross domestic product and is expected to top 16% by 2020. After recent inquiries into the failings of its public health system, the Queensland Government has committed itself to a 25% increase in expenditure on health over the next 5 years. But will it lead to better population health, and is it sustainable? The return-on-investment curve for modern health care may be flattening out, in an environment of growing numbers of older patients with chronic illnesses, maldistribution of services and hospital overcrowding. A change in thinking is required if current medical practice is to avoid imploding when confronted with the next major economic downturn. Health policy, service funding and clinical training must focus on critical appraisal of the effectiveness of health care technologies and the structure and financing of health care systems. Practising clinicians will be obliged to provide leadership in determining value for money in the choice of health care for specific patient populations and how that care is delivered.

Appraising qualitative research for inclusion in systematic reviews:A quantitative and qualitative comparison of three methods

Objective: Qualitative research is increasingly valued as part of the evidence for policy and practice, but how it should be appraised is contested. Various appraisal methods, including checklists and other structured approaches, have been proposed but rarely evaluated. We aimed to compare three methods for appraising qualitative research papers that were candidates for inclusion in a systematic review of evidence on support for breast-feeding. Method: A sample of 12 research papers on support for breast-feeding was appraised by six qualitative reviewers using three appraisal methods: unprompted judgement, based on expert opinion; a UK Cabinet Office quality framework; and CASP, a Critical Appraisal Skills Programme tool. Papers were assigned, following appraisals, to 1 of 5 categories, which were dichotomized to indicate whether or not papers should be included in a systematic review. Patterns of agreement in categorization of papers were assessed quantitatively using κ statistics, and qualitatively using cross-case analysis. Results: Agreement in categorizing papers across the three methods was slight (κ =0.13; 95% CI 0.06-0.24). Structured approaches did not appear to yield higher agreement than that by unprompted judgement. Qualitative analysis revealed reviewers' dilemmas in deciding between the potential impact of findings and the quality of the research execution or reporting practice. Structured instruments appeared to make reviewers more explicit about the reasons for their judgements. Conclusions: Structured approaches may not produce greater consistency of judgements about whether to include qualitative papers in a systematic review. Future research should address how appraisals of qualitative research should be incorporated in systematic reviews. © The Royal Society of Medicine Press Ltd 2007.

Patients’ and health professionals’ views and experiences of atrial fibrillation and oral-anticoagulant therapy:a qualitative meta-synthesis

Objective - Atrial fibrillation (AF) patients are prescribed oral-anticoagulant (OAC) therapy, often warfarin, to reduce stroke risk. We explored existing qualitative evidence about patients’ and health professionals’ experiences of OAC therapy. Methods - Systematic searches of eight bibliographic databases were conducted. Quality was appraised using the Critical Appraisal Skills Programme tool and data from ten studies were synthesised qualitatively. Results - Four third-order constructs, emerged from the final step in the analysis process: (1) diagnosing AF and the communication of information, (2) deciding on OAC therapy, (3) challenges revolving around patient issues, and (4) healthcare challenges. Synthesis uncovered perspectives that could not be achieved through individual studies. Conclusion - Physicians’ and patients’ experiences present a dichotomy of opinion on decision-making, which requires further exploration and changes in practice. Outcomes of workload pressure on both health professionals and patients should be investigated. The need for on-going support and education to patients and physicians is critical to achieve best practice and treatment adherence. Practice implications - Such research could encourage health professionals to understand and attend better to the needs and concerns of the patient. Additionally these findings can be used to inform researchers and healthcare providers in developing educational interventions with both patients and health professionals.

Joint tenancies and English commorientes:a question of survivorship or severance?

The aim of this article is to provide a critical appraisal of the English law in relation to the doctrine of commorientes with particular reference to its implications in respect of property held on a joint tenancy. The article suggests a measure of reform which would produce a fairer dsitribution of joint property in circusmtances where all joint tenants have died in a common disaster and it cannot be ascertained which joint tenant died first.

Systematic review investigating the reporting of comorbidities and medication in randomized controlled trials of people with dementia

Objectives: dementia is a debilitating condition characterised by global loss of cognitive and intellectual functioning, which reduces social and occupational performance. This population frequently presents with medical co-morbidities such as hypertension, cardiovascular disease and diabetes. The CONSORT statement outlines recommended guidance on reporting of participant characteristics in clinical trials. It is, however, unclear how much these are adhered to in trials assessing people with dementia. This paper assesses the reporting of medical co-morbidities and prescribed medications for people with dementia within randomised controlled trial (RCT) reports. Design: a systematic review of the published literature from the databases AMED, CINAHL, MEDLINE, EMBASE and the Cochrane Clinical Trial Registry from 1 January 1997 to 9 January 2014 was undertaken in order to identify RCTs detailing baseline medical co-morbidities and prescribed medications . Eligible studies were appraised using the Critical Appraisal Skills Programme (CASP) RCT appraisal tool, and descriptive statistical analyses were calculated to determine point prevalence. Results: nine trials, including 1474 people with dementia, were identified presenting medical co-morbidity data. These indicated neurological disorders ( prevalence 91%), vascular disorders (prevalence 91%), cardiac disorders ( prevalence 74%) and ischaemic cerebrovascular disease ( prevalence 53%) were most frequently seen. Conclusions: published RCTs poorly report medical co-morbidities and medications for people with dementia. Future trials should include the report of these items to allow interpretation of whether the results are generalisable to frailer older populations.

Policy Framework and Roadmap for Open Access, Open Research Data and Open Science

Overview of the growth of policies and a critical appraisal of the issues affecting open access, open data and open science policies. Example policies and a roadmap for open access, open research data and open science are included.