Researching pre-term birth: the oracle trial and children study

Researching pre-term birth: the oracle trial and children stud

Concesión de viático a don Phelipe de Hughs, sacerdote irlandés, para ir a la Misión de Irlanda

Fecha del documento: 1745-06-15. 4 páginasMemorial de don Felipe Hughs, misionero, que ha acabado sus estudios y ha sido llamado por su prelado a la Santa Misión de su perseguida patria, solicitando para ello el acostumbrado viático. Certificación impresa en latín, con sello de la Compañía de Jesús, de José Gómez, Rector del Colegio de Sevilla, acreditando los estudios realizados por el solicitante. Envío del marqués de la Ensenada del memorial al R.P. Jaime Antonio Fevre, que está de acuerdo con la concesión del viático. Respuesta final: "S.M. viene en ello"Proyecto Proyección Política y Social de la Comunidad Irlandesa en la Monarquía hispánica y en la América Colonial de la Edad Moderna(siglos XVI-XVIII) (HAR2009-11339 - subprograma HIST) del Ministerio de Economía y Competitividad en colaboración con el Consejo Superior de Investigaciones Científicas (CSIC), Embajada de Irlanda en Madrid, National University of Ireland (NUI) Maynooth, University College Dublin y Trinity College DublinDon Phelipe de HughsFelipe VCompañía de JesúsSí100 ducadosSíN

Consort diagram for the ELSIPS follow up.

<p>Consort diagram for the ELSIPS follow up.</p

ELSIPS sollow up sample composition and characteristics.

<p>ELSIPS sollow up sample composition and characteristics.</p

Group differences by randomisation in the ELSIPS follow up study at 12 months postpartum.

<p>Group differences by randomisation in the ELSIPS follow up study at 12 months postpartum.</p

Baseline data for ELSIPS follow up sample compared to a) all participants who were eligible to be followed but who were not followed and b) all participants who were not followed.

<p>Baseline data for ELSIPS follow up sample compared to a) all participants who were eligible to be followed but who were not followed and b) all participants who were not followed.</p

Consent revisited: The impact of return of results on participants’ views and expectations about trial participation.

Background Increasingly, the sharing of study results with participants is advocated as an element of good research practice. Yet little is known about how receiving the results of trials may impact on participants’ perceptions of their original decision to consent. Objective We explored participants’ views of their decision to consent in a clinical trial after they received results showing adverse outcomes in some arms of the trial. Method Semi-structured interviews were conducted with a purposive sample of 38 women in the UK who participated in a trial of antibiotics in pregnancy. All had received results from a follow-up study that reported increased risk of adverse outcomes for children of participants in some intervention arms. Data analysis was based on the constant comparative method. Results Participants’ original decisions to consent to the trial had been based on hope of personal benefit and assumptions of safety. On receiving the results, most made sense of their experience in ways that enabled them to remain content with their decision to take part. But for some, the results provoked recognition that their original expectations might have been mistaken or that they had not understood the implications of their decision to participate. These participants experienced guilt, a sense of betrayal by the maternity staff and researchers involved in the trial, and damage to trust. Conclusions Sharing of study results is not a wholly benign practice, and requires careful development of suitable approaches for further evaluation before widespread adoption

Unblinding following trial participation: Qualitative study of participants' perspectives.

Background: The implications of offering unblinding to trial participants to treatment arm after trial completion have been little explored. Purpose: We sought to explore trial participants’ perspectives on whether they would like to be unblinded as to the treatment arm to which they were allocated following involvement in a large randomised controlled trial (RCT). Methods: We conducted semi-structured interviews with 38 women who had participated in a trial during suspected preterm labour and had received the results of a long-term follow-up study that identified adverse outcomes for children in some of the treatment groups. Participants were sampled purposively. Analysis was based on the constant comparative method. Results: Most women reported that they wanted to know the treatment arm to which they had been allocated. While the primary motive for some was curiosity, many others wanted to know as part of an attempt to understand or explain their child’s current health problems. These women were motivated by a search for a coherent causal narrative, even though unblinding was unlikely to be able to meet their aspirations. Some participants identified potential disadvantages in discovering their treatment allocation, including feeling responsible for their child’s health status, and some women were very clear that they did not want to know their treatment group. Limitations: A purposive sample was used and the extent to which it represents the views of all participants in the study is not established. Conclusions Important challenges arise in offering to unblind trial participants, whatever the trial results. Participants may need help and support to understand the limitations of the knowledge they gain through being unblinded and to decide whether they wish to know to which treatment arm they were allocated

Caracterización de biomarcadores en la recurrencia post-quirúrgica de la enfermedad de Crohn: valor predictivo e implicación patogénica

A pesar de un conocimiento cada vez mayor sobre la patogenia de la enfermedad de Crohn (EC) y el desarrollo de esquemas de tratamiento más potentes que incluyen los fármacos biológicos, las tasas de cirugía en estos pacientes siguen siendo elevadas. Así, un 50-60% de los pacientes con EC requieren de una resección intestinal en los primeros 10 años tras el diagnóstico, y un 25% de éstos acabarán requiriendo de una segunda cirugía dentro de los 5 años siguientes. Dado que la cirugía no supone un tratamiento curativo, la reaparición de lesiones tras la resección de todo el tramo intestinal afecto (fenómeno conocido como recurrencia post-quirúrgica) es muy frecuente en estos pacientes, a pesar incluso de la intervención terapéutica. Entre los tratamientos empleados para prevenir la recurrencia de la EC se incluyen la mesalazina, los inmunomoduladores tiopurínicos y en la actualidad los fármacos biológicos o anti-TNF. En los últimos años, diferentes estudios han confirmado la eficacia del tratamiento biológico en la prevención de la recurrencia, especialmente en pacientes de alto riesgo, con una tendencia actual a su introducción precoz tras la cirugía. Sin embargo, estos tratamientos implican una tasa nada desdeñable de efectos adversos, además de un elevado coste por paciente. Por otro lado, no está claramente establecido qué pacientes se benefician de un tratamiento más intensivo tras la cirugía ni la duración de mantenimiento del mismo. Por todo ello, surge la necesidad de desarrollar nuevas herramientas y estrategias que permitan identificar el riesgo de una recurrencia precoz tras la cirugía y optimizar el manejo clínico de estos pacientes. En el momento actual, la ileocolonoscopia continúa siendo el gold estándar para el seguimiento y diagnóstico de la recurrencia, a pesar de suponer una técnica invasiva, costosa, no exenta de riesgos y en general mal tolerada por los pacientes. Esto es así porque hasta el momento no disponemos de buenos marcadores predictores de recurrencia tras la cirugía, y porque la utilidad de la valoración clínica y analítica para el diagnóstico de la recurrencia es limitada. Por este motivo, existe especial interés en el empleo de biomarcadores no invasivos y de fácil obtención, que sirvan para monitorizar a estos pacientes tras la cirugía y permitan detectar precozmente el desarrollo de recurrencia. En este sentido, entre los marcadores fecales, la calprotectina ha mostrado previamente gran utilidad clínica en diferentes escenarios de la enfermedad y, aunque su papel en el contexto post-quirúrgico no ha sido evaluado en profundidad en series amplias de carácter prospectivo, la evidencia disponible sugiere también su utilidad como marcador de recurrencia, aunque quedan aspectos por definir con claridad para su aplicación en la práctica. La existencia de otros posibles biomarcadores en sangre periférica tampoco ha sido explorada en este escenario de la EC. Por otro lado, el escenario clínico de la recurrencia supone una condición patogénica de novo, por lo que los pacientes con EC intervenidos constituyen el mejor modelo natural in vivo para poder estudiar e identificar los posibles mecanismos patogénicos implicados en la reaparición de la enfermedad. Con todo ello, el objetivo de la presente tesis doctoral se centra en la caracterización prospectiva de marcadores no invasivos, a partir de muestras biológicas de fácil obtención (sangre periférica y heces), que dispongan de capacidad predictiva de recurrencia en el contexto post-quirúrgico de la EC, y permitan identificar y monitorizar los cambios que acontecen en el desarrollo de la inflamación de novo. Igualmente, se pretende conocer el perfil de la respuesta inmune que dirige este proceso y los posibles elementos epigenéticos reguladores, así como su implicación patogénica en la génesis de la recurrencia. Finalmente, se plantea el desarrollo de una herramienta de predicción (índice predictivo combinado) empleando los biomarcadores identificados, con potencial aplicación en la práctica clínica para un mejor manejo de estos pacientes.Despite increasing awareness of the pathogenesis of Crohn's disease (CD) and the development of more potent therapeutic regimens including biological drugs, surgery rates in these patients remain high. Thus, 50-60% of patients with CD require bowel resection in the first 10 years after diagnosis, and 25% of these patients will require a second surgery within the next 5 years. Since surgery is not curative, the appearance of new intestinal lesions after resection is very frequent in these patients despite the therapeutic intervention. This phenomenon is known as post-operative recurrence. Treatments used to prevent recurrence of CD after surgery include mesalazine, thiopurines, and nowadays, biological or anti-TNF drugs. In recent years, several studies have confirmed the efficacy of biological treatment in the prevention of recurrence, especially in high-risk patients, with a current trend towards their early introduction after surgery. However, these drugs imply a not insignificant rate of adverse effects, in addition to a high cost per patient. On the other hand, it is not clearly established which patients benefit from a more intensive treatment after surgery or the duration of maintenance of the same. Therefore, the need arises to develop new tools and strategies to identify the risk of an early recurrence and to optimize the clinical management of these patients. Currently, ileocolonoscopy continues to be the gold standard for the follow-up and diagnosis of recurrence, despite being an invasive technique, expensive, non-risk-free and generally poorly tolerated by patients. This is because we do not have good predictive markers of recurrence after surgery until now, and because the usefulness of clinical and analytical assessment for the diagnosis of recurrence is limited. For this reason, there is a special interest in the use of non-invasive and easily obtained biomarkers, which serve to monitor these patients after surgery and allow early detection of post-operative recurrence. In this sense, fecal markers such as calprotectin have previously shown great clinical utility in different scenarios of the disease. In the post-surgical context, available evidence also suggests its potential utility as a marker of recurrence, although some aspects for its application in clinical practice remain to be clearly defined. Other possible biomarkers in peripheral blood have also not been explored in this EC scenario. On the other hand, post-operative recurrence supposes a new pathogenic condition, so that the CD patients underwent surgery are the best natural model in vivo to study and identify the pathogenic mechanisms involved in the reappearance of the disease. The aim of the present study is the prospective characterization of non-invasive markers in peripheral blood and feces, which have a predictive capacity for post-operative recurrence in CD, to identify and monitor the changes that occur in the development of the novo inflammation. Likewise, we intend to know the profile of the immune response that leads this process and possible regulatory epigenetic elements, as well as its pathogenic implication in the genesis of recurrence. Finally, we propose the development of a predictive tool (predictive combined index) using the identified biomarkers, with potential application in clinical practice for a better management of these patients

Additional file 1: of The design and implementation of an obstetric triage system for unscheduled pregnancy related attendances: a mixed methods evaluation

Baseline characteristics of women who attended Triage (DOCX 190 kb