On the normativity of evidence - Lessons from philosophy of science and the "VALIDATE" project.

"Evidence" is a key term in medicine and health services research, including Health Technology Assessment (HTA). Randomized clinical trials (RCTs) have undoubtedly dominated the scene of generating evidence for a long period of time, becoming the hallmark of evidence-based medicine (EBM). However, due to a number of misunderstandings, the lay audience and some researchers have sometimes placed too much trust in RCTs compared to other methods of investigation. One of the principal misunderstandings is to consider RCTs findings as isolated and self-apparent pieces of information. In other words, what has been essentially lacking was the awareness of the value-context of the evidence and, in particular, the value- and theory-ladenness (normativity) of scientific knowledge. This paper aims to emphasize the normativity that exists in the production of scientific knowledge, and in particular in the conduct of RCTs as well as in the performance of HTA. The work is based on some lessons learned from Philosophy of Science and the European project "VALIDATE" (VALues In Doing Assessments of healthcare TEchnologies"). VALIDATE was a three-year EU Erasmus+ strategic partnerships project (2018-2021), in which training in the field of HTA was further optimized by using insights from political science and ethics (in accordance with the recent definition of HTA). Our analysis may reveal useful insights for addressing some challenges that HTA is going to face in the future.

Sumario de las recomendaciones y puntos clave del Consenso de las Sociedades Científicas Españolas (SEPAR, SEMICYUC, SEMES; SECIP, SENeo, SEDAR, SENP) para la utilización de la ventilación no invasiva y terapia de alto flujo con cánulas nasales en el paciente adulto, pediátrico y neonatal con insuficiencia respiratoria aguda grave / Summary of recommendations and key points of the consensus of Spanish scientific societies (SEPAR, SEMICYUC, SEMES; SECIP, SENEO, SEDAR, SENP) on the use of non-invasive ventilation and high-flow oxygen therapy with nasal cannulas in adult, pediatric, and neonatal patients with severe acute respiratory failure

El soporte respiratorio no invasivo (SRNI) comprende 2 modalidades de tratamiento, la ventilación mecá-nica no invasiva (VMNI) y la terapia de alto flujo con cánulas nasales (TAFCN) que se aplican en pacientes adultos, pediátricos y neonatales con insuficiencia respiratoria aguda (IRA). Sin embargo, el grado de acuerdo entre las distintas especialidades sobre el beneficio de estas técnicas en diferentes escenarios clínicos es controvertido. El objetivo del presente consenso fue elaborar una serie de recomendaciones de buena práctica clínica para la aplicación de soporte no invasivo en pacientes con IRA, avaladas por todas las sociedades científicas involucradas en el manejo del paciente adulto y pediátrico/neonatal con IRA. Para ello se contactó con las diferentes sociedades implicadas, quienes designaron a su vez a un grupo de 26 profesionales con suficiente experiencia en su aplicación. Se realizaron 3 reuniones presenciales para consensuar las recomendaciones (hasta un total de 71) fundamentadas en la revisión de la literatura y en la actualización de la evidencia disponible en relación con 3 categorías: indicaciones, monitorización yseguimiento del SRNI. Finalmente, se procedió a votación telemática de cada una de las recomendaciones, por parte de los expertos de cada sociedad científica implicada. Para la clasificación del grado de acuerdo se optó por un sistema analógico de clasificación fácil e intuitivo de usar, y que expresara con claridad si el procedimiento relacionado con el SRNI debía hacerse, podía hacerse o no debía hacerse. (AU)

Non-invasive respiratory support (NIRS) in adult, pediatric, and neonatal patients with acute respiratory failure (ARF) comprises two treatment modalities, non-invasive mechanical ventilation (NIMV) and high-flow nasal cannula (HFNC) therapy. However, experts from different specialties disagree on the benefit of these techniques in different clinical settings. The objective of this consensus was to develop a series of good clinical practice recommendations for the application of non-invasive support in patients with ARF, endorsed by all scientific societies involved in the management of adult and pediatric/neonatal patients with ARF. To this end, the different societies involved were contacted, and they in turn appointed a group of 26 professionals with sufficient experience in the use of these techniques. Three face-to-face meetings were held to agree on recommendations (up to a total of 71) based on a literature review and the latest evidence associated with 3 categories: indications, monitoring and follow-up of NIRS. Finally, the experts from each scientific society involved voted telematically on each of the recommendations. To classify the degree of agreement, an analogue classification system was chosen that was easy and intuitive to use and that clearly stated whether the each NIRS intervention should be applied, could be applied, or should not be applied. (AU)

Summary of recommendations and key points of the consensus of Spanish scientific societies (SEPAR, SEMICYUC, SEMES; SECIP, SENEO, SEDAR, SENP) on the use of non-invasive ventilation and high-flow oxygen therapy with nasal cannulas in adult, pediatric, and neonatal patients with severe acute respiratory failure.

Non-invasive respiratory support (NIRS) in adult, pediatric, and neonatal patients with acute respiratory failure (ARF) comprises two treatment modalities, non-invasive mechanical ventilation (NIMV) and high-flow nasal cannula (HFNC) therapy. However, experts from different specialties disagree on the benefit of these techniques in different clinical settings. The objective of this consensus was to develop a series of good clinical practice recommendations for the application of non-invasive support in patients with ARF, endorsed by all scientific societies involved in the management of adult and pediatric/neonatal patients with ARF. To this end, the different societies involved were contacted, and they in turn appointed a group of 26 professionals with sufficient experience in the use of these techniques. Three face-to-face meetings were held to agree on recommendations (up to a total of 71) based on a literature review and the latest evidence associated with 3 categories: indications, monitoring and follow-up of NIRS. Finally, the experts from each scientific society involved voted telematically on each of the recommendations. To classify the degree of agreement, an analogue classification system was chosen that was easy and intuitive to use and that clearly stated whether the each NIRS intervention should be applied, could be applied, or should not be applied.

Summary of recommendations and key points of the consensus of Spanish scientific societies (SEPAR, SEMICYUC, SEMES; SECIP, SENEO, SEDAR, SENP) on the use of non-invasive ventilation and high-flow oxygen therapy with nasal cannulas in adult, pediatric, and neonatal patients with severe acute respiratory failure. / Sumario de las recomendaciones y puntos clave del Consenso de las Sociedades Científicas Españolas (SEPAR, SEMICYUC, SEMES; SECIP, SENeo, SEDAR, SENP) para la utilización de la ventilación no invasiva y terapia de alto flujo con cánulas nasales en el paciente adulto, pediátrico y neonatal con insuficiencia respiratoria aguda grave.

Non-invasive respiratory support (NIRS) in adult, pediatric, and neonatal patients with acute respiratory failure (ARF) comprises two treatment modalities, non-invasive mechanical ventilation (NIMV) and high-flow nasal cannula (HFNC) therapy. However, experts from different specialties disagree on the benefit of these techniques in different clinical settings. The objective of this consensus was to develop a series of good clinical practice recommendations for the application of non-invasive support in patients with ARF, endorsed by all scientific societies involved in the management of adult and pediatric/neonatal patients with ARF. To this end, the different societies involved were contacted, and they in turn appointed a group of 26 professionals with sufficient experience in the use of these techniques. Three face-to-face meetings were held to agree on recommendations (up to a total of 71) based on a literature review and the latest evidence associated with 3 categories: indications, monitoring and follow-up of NIRS. Finally, the experts from each scientific society involved voted telematically on each of the recommendations. To classify the degree of agreement, an analogue classification system was chosen that was easy and intuitive to use and that clearly stated whether the each NIRS intervention should be applied, could be applied, or should not be applied.

Workshop Report: concepts and methods in the economics of nutrition--gateways to better economic evaluation of nutrition interventions.

Improving health through better nutrition of the population may contribute to enhanced efficiency and sustainability of healthcare systems. A recent expert meeting investigated in detail a number of methodological aspects related to the discipline of nutrition economics. The role of nutrition in health maintenance and in the prevention of non-communicable diseases is now generally recognised. However, the main scope of those seeking to contain healthcare expenditures tends to focus on the management of existing chronic diseases. Identifying additional relevant dimensions to measure and the context of use will become increasingly important in selecting and developing outcome measurements for nutrition interventions. The translation of nutrition-related research data into public health guidance raises the challenging issue of carrying out more pragmatic trials in many areas where these would generate the most useful evidence for health policy decision-making. Nutrition exemplifies all the types of interventions and policy which need evaluating across the health field. There is a need to start actively engaging key stakeholders in order to collect data and to widen health technology assessment approaches for achieving a policy shift from evidence-based medicine to evidence-based decision-making in the field of nutrition.

Public health genomics in Spain: the status of a non-existing reality.

AIMS: The Public Health Genomics European Network (PHGEN) aimed, among other objectives, to identify the geographical variability and legal barriers of genomic medicine and public health genomics (PHG) at an international market, where the lack of policy coherence may limit its development in Europe. PHGEN supported the creation of National Task Forces (NTF) to overview the national settings and identify proposals in different European countries. Here we summarize the key issues which emerged during the discussions conducted within the Spanish NTF. METHODS: The Spanish NTF is composed of 25 experts and key leaders in PHG-related areas of knowledge and met 3 times between January 2007 and 2008 to identify, discuss and propose recommendations for the development and use of PHG in Spain. Discussions were recorded and shared with participants for amendments. RESULTS: We observed lack of applied knowledge on PHG, training skills and capacities on genomics of the involved specialists (gynecology, pediatrics, oncology, etc.), lack of applied research on diagnostics and knowledge on the topic in the population and mass media. Some promoting factors were observed, such as plans on genetics in the different regional autonomous communities, guidance on the introduction of genomic technologies and the new regional health technology regulatory frameworks. CONCLUSION: Although there is a current Spanish regulatory framework for the introduction of health technologies and a published biomedical law that could be useful for the development of PHG in Spain, specific and tailored initiatives should be promoted by regional and national authorities to improve the accreditation professionals and to inform the citizens on genomic technologies in order to empower them.

Leukocytapheresis for steroid-dependent ulcerative colitis in clinical practice: results of a nationwide Spanish registry.

BACKGROUND: Several small, prospective, open studies suggest that leukocytapheresis might be efficient in patients with steroid-dependent ulcerative colitis (UC). AIM: To evaluate the short- and long-term effectiveness of leukocytapheresis for the management of steroid-dependent UC in clinical practice. METHODS: A Web-based, nationwide database specifically designed to record the efficacy and safety data of leukocytapheresis therapy in UC was available from September 2007 in Spain. Clinical data were collected at treatment baseline, 1 month after the last apheresis session (initial efficacy), and 6 and 12 months thereafter (long-term efficacy). Remission was defined as a Mayo Clinic index ≤2 together with complete steroid withdrawal and response as a decrease of ≥3 from the baseline score. RESULTS: A total of 142 steroid-dependent UC patients were included in the registry, most of them treated with the Adacolumn™ system. In 69% of patients thiopurine therapy failed to achieve steroid-free clinical remission. Initial clinical remission was obtained in 37% of cases. The initial corticosteroid dose, the number and frequency of apheresis sessions, or the previous failure of thiopurines and/or infliximab did not influence the initial remission rate, but a greater decrease in CRP levels was associated with a higher probability to obtain initial remission. At 6 and 12 months, 41 and 36% of patients were in clinical remission, respectively. Only one serious adverse effect was recorded. CONCLUSIONS: In clinical practice, apheresis allows long-term steroid-free clinical remission in up to one third of steroid-dependent UC patients, even in those with prior failure of thiopurines.

Nutrition economics - characterising the economic and health impact of nutrition.

There is a new merging of health economics and nutrition disciplines to assess the impact of diet on health and disease prevention and to characterise the health and economic aspects of specific changes in nutritional behaviour and nutrition recommendations. A rationale exists for developing the field of nutrition economics which could offer a better understanding of both nutrition, in the context of having a significant influence on health outcomes, and economics, in order to estimate the absolute and relative monetary impact of health measures. For this purpose, an expert meeting assessed questions aimed at clarifying the scope and identifying the key issues that should be taken into consideration in developing nutrition economics as a discipline that could potentially address important questions. We propose a first multidisciplinary outline for understanding the principles and particular characteristics of this emerging field. We summarise here the concepts and the observations of workshop participants and propose a basic setting for nutrition economics and health outcomes research as a novel discipline to support nutrition, health economics and health policy development in an evidence and health-benefit-based manner.

GABAergic neurons in the rabbit visual cortex: percentage, layer distribution and cortical projections.

6250 neurons yielding either callosal or inter-areal ipsilateral projections extrinsic to area 17 was GABAergic. Comparing these findings with those reported for other mammals, it seems that the incidence and distribution of GABAergic neurons in the visual cortex is similar in rabbits and rats. In contrast to rats but akin to higher mammals, no GABAergic neuron was found to furnish cortico-cortical connections to area 17 other than intrinsic connections.

Percentage incidence of gamma-aminobutyric acid neurons in the claustrum of the rabbit and comparison with the cortex and putamen.

We describe the incidence of gamma-aminobutyric acid (GABA)ergic neurons after post-embedding immunocytochemistry on semithin sections of the claustrum, putamen and lateral, dorsal and medial cortical areas. Twelve percent of the neurons counted in the claustrum of 11 rabbits were GABAergic. This incidence was significantly higher in the dorsal halves of both the insular and endopiriform claustra than in the ventral (13 vs. 10%). The incidence of GABAergic cells was 4% in the putamen, 14% in the insular cortex, 15% in areas 17 and 18 and 13% in area 29d. Thus, our results indicate that in contrast to the putamen the incidence of GABAergic cells was similar in the claustrum and cortical areas. We interpret this in the light of the pallial origin of the claustrum, which has recently been substantiated.

GABAergic neurons with AMPA GluR1 and GluR2/3 immunoreactivity in the rat striate cortex.

The co-localization of GABA with AMPA receptor subunits GluR1 or GluR2/3 was analysed in the striate cortex of adult rats by post-embedding immunocytochemistry in semithin sections. Adjacent 1 micron semithin sections of four brains were alternately incubated with specific antibodies against GABA and the GluR1 and GluR2/3 subunits. The post-embedding immunocytochemistry showed that 38% of GABAergic neurons contained the GluR1 subunit and 10% contained the GluR2/3 subunits. Previous work has shown GluR1 immunoreactivity in non-pyramidal neurons and GluR2/3 immunoreactivity in pyramidal neurons. However, this study is the first to demonstrate that there are GABAergic neurons co-localized with GluR2/3 AMPA subunits. Additionally, this study provides quantitative estimations of the laminar distribution of GABAergic and non-GABAergic cells containing the AMPA GluR1 and GluR2/3 subunits.