Design, implementation and usability analysis of patient empowerment in ADLIFE project via patient reported outcome measures and shared decision making

Introduction: This paper outlines the design, implementation, and usability study results of the patient empowerment process for chronic disease management, using Patient Reported Outcome Measurements and Shared Decision-Making Processes. Background: The ADLIFE project aims to develop innovative, digital health solutions to support personalized, integrated care for patients with severe long-term conditions such as Chronic Obstructive Pulmonary Disease, and/or Chronic Heart Failure. Successful long-term management of patients with chronic conditions requires active patient self-management and a proactive involvement of patients in their healthcare and treatment. This calls for a patient-provider partnership within an integrated system of collaborative care, supporting self-management, shared-decision making, collection of patient reported outcome measures, education, and follow-up. Methods: ADLIFE follows an outcome-based and patient-centered approach where PROMs represent an especially valuable tool to evaluate the outcomes of the care delivered. We have selected 11 standardized PROMs for evaluating the most recent patients’ clinical context, enabling the decision-making process, and personalized care planning. The ADLIFE project implements the "SHARE approach’ for enabling shared decision-making via two digital platforms for healthcare professionals and patients. We have successfully integrated PROMs and shared decision-making processes into our digital toolbox, based on an international interoperability standard, namely HL7 FHIR. A usability study was conducted with 3 clinical sites with 20 users in total to gather feedback and to subsequently prioritize updates to the ADLIFE toolbox. Results: User satisfaction is measured in the QUIS7 questionnaire on a 9-point scale in the following aspects: overall reaction, screen, terminology and tool feedback, learning, multimedia, training material and system capabilities. With all the average scores above 6 in all categories, most respondents have a positive reaction to the ADLIFE PEP platform and find it easy to use. We have identified shortcomings and have prioritized updates to the platform before clinical pilot studies are initiated. Conclusions: Having finalized design, implementation, and pre-deployment usability studies, and updated the tool based on further feedback, our patient empowerment mechanisms enabled via PROMs and shared decision-making processes are ready to be piloted in clinal settings. Clinical studies will be conducted based at six healthcare settings across Spain, UK, Germany, Denmark, and Israel

Design, implementation and usability analysis of patient empowerment in ADLIFE project via patient reported outcome measures and shared decision making

Introduction: This paper outlines the design, implementation, and usability study results of the patient empowerment process for chronic disease management, using Patient Reported Outcome Measurements and Shared Decision-Making Processes. Background: The ADLIFE project aims to develop innovative, digital health solutions to support personalized, integrated care for patients with severe long-term conditions such as Chronic Obstructive Pulmonary Disease, and/or Chronic Heart Failure. Successful long-term management of patients with chronic conditions requires active patient self-management and a proactive involvement of patients in their healthcare and treatment. This calls for a patient-provider partnership within an integrated system of collaborative care, supporting self-management, shared-decision making, collection of patient reported outcome measures, education, and follow-up. Methods: ADLIFE follows an outcome-based and patient-centered approach where PROMs represent an especially valuable tool to evaluate the outcomes of the care delivered. We have selected 11 standardized PROMs for evaluating the most recent patients’ clinical context, enabling the decision-making process, and personalized care planning. The ADLIFE project implements the "SHARE approach’ for enabling shared decision-making via two digital platforms for healthcare professionals and patients. We have successfully integrated PROMs and shared decision-making processes into our digital toolbox, based on an international interoperability standard, namely HL7 FHIR. A usability study was conducted with 3 clinical sites with 20 users in total to gather feedback and to subsequently prioritize updates to the ADLIFE toolbox. Results: User satisfaction is measured in the QUIS7 questionnaire on a 9-point scale in the following aspects: overall reaction, screen, terminology and tool feedback, learning, multimedia, training material and system capabilities. With all the average scores above 6 in all categories, most respondents have a positive reaction to the ADLIFE PEP platform and find it easy to use. We have identified shortcomings and have prioritized updates to the platform before clinical pilot studies are initiated. Conclusions: Having finalized design, implementation, and pre-deployment usability studies, and updated the tool based on further feedback, our patient empowerment mechanisms enabled via PROMs and shared decision-making processes are ready to be piloted in clinal settings. Clinical studies will be conducted based at six healthcare settings across Spain, UK, Germany, Denmark, and Israel

Hypothesized role of pregnancy hormones on HER2+breast tumor development

Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies >/=1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR- = ER- and PR-) expression and HER2 status: HR+/HER2-, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2- tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2- cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of 45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08-2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors

Neuregulin-1 promotes functional improvement by enhancing collateral sprouting in SOD1G93A ALS mice and after partial muscle denervation

Altres ajuts: Fundació La Marato-TV3(TV3201428-10), AFM-Telethon (Nrg14ALS)Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of motoneurons, which is preceded by loss of neuromuscular connections in a "dying back" process. Neuregulin-1 (Nrg1) is a neurotrophic factor essential for the development and maintenance of neuromuscular junctions, and Nrg1 receptor ErbB4 loss-of-function mutations have been reported as causative for ALS. Our main goal was to investigate the role of Nrg1 type I (Nrg1-I) in SOD1G93A mice muscles. We overexpressed Nrg1-I by means of an adeno-associated viral (AAV) vector, and investigated its effect by means of neurophysiological techniques assessing neuromuscular function, as well as molecular approaches (RT-PCR, western blot, immunohistochemistry, ELISA) to determine the mechanisms underlying Nrg1-I action. AAV-Nrg1-I intramuscular administration promoted motor axon collateral sprouting by acting on terminal Schwann cells, preventing denervation of the injected muscles through Akt and ERK1/2 pathways. We further used a model of muscle partial denervation by transecting the L4 spinal nerve. AAV-Nrg1-I intramuscular injection enhanced muscle reinnervation by collateral sprouting, whereas administration of lapatinib (ErbB receptor inhibitor) completely blocked it. We demonstrated that Nrg1-I plays a crucial role in the collateral reinnervation process, opening a new window for developing novel ALS therapies for functional recovery rather than preservation

Factors associated with Toxoplasma gondii infection in confined farrow-to-finish pig herds in western France: an exploratory study in 60 herds

Background: Infection by Toxoplasma gondii postnatally can occur after ingestion of contaminated meat or water (tissue cysts/oocysts). In Europe, percentage of meat borne infections is estimated between 30 and 63 %, out of which pork makes the most important source. The aim of this study was to (i) investigate the seroprevalence of T. gondii in intensive pig farms from western France; and (ii) identify the risk factors associated with seropositivity. Methods: Data were collected between November 2006 and February 2008 in 60 intensive farrow-to-finish farms, where sera were taken from 3595 fattening pigs, weaned and suckling piglets. Information about three classes of potential seropositivity risk factors were obtained through a questionnaire concerning: (i) breeding characteristics; (ii) farm management; and (iii) husbandry and hygiene. The modified agglutination test (MAT) was used for detection of specific anti T. gondii antibodies in pig sera, starting from 1/6 dilution. Results: The overall proportion of seropositive animals was 6.9 %, but the proportion of herds with at least one positive pig was 100 %. Multivariate logistic mixed model showed an increased seropositivity risk in weaned compared to suckling piglets, and a decreasing risk for mid-sized and large farms. The presence of a Danish entry facility, that clearly separates clean and dirty areas, had a protective effect on T. gondii seropositivity as well. Conclusions: The observed proportion of herds with at least one T. gondii seropositive animal provides further evidence that even in confined conditions of pig breeding, infection occurs, and is common. The highest risk for acquiring T. gondii is at the end of weaning period. Smaller confined pig farms demonstrate higher T. gondii seropositivity levels. This study also showed that Danish entry on farm buildings provides effective protection against T. gondii

The Rise and Fall of "Respectable" Spanish Liberalism, 1808-1923: An Explanatory Framework

The article focuses on the reasons behind both the consolidation of what I have termed “respectable” liberalism between the 1830s and the 1840s and its subsequent decline and fall between 1900 and 1923. In understanding both processes I study the links established between “respectable” liberals and propertied elites, the monarchy, and the Church. In the first phase these links served to consolidate the liberal polity. However, they also meant that many tenets of liberal ideology were compromised. Free elections were undermined by the operation of caciquismo, monarchs established a powerful position, and despite the Church hierarchy working with liberalism, the doctrine espoused by much of the Church was still shaped by the Counter-Reformation. Hence, “respectable” liberalism failed to achieve a popular social base. And the liberal order was increasingly denigrated as part of the corrupt “oligarchy” that ruled Spain. Worse still, between 1916 and 1923 the Church, monarch, and the propertied elite increasingly abandoned the liberal Monarchist Restoration. Hence when General Primo de Rivera launched his coup the rug was pulled from under the liberals’ feet and there was no one to cushion the fall

Overview of recent TJ-II stellarator results

The main results obtained in the TJ-II stellarator in the last two years are reported. The most important topics investigated have been modelling and validation of impurity transport, validation of gyrokinetic simulations, turbulence characterisation, effect of magnetic configuration on transport, fuelling with pellet injection, fast particles and liquid metal plasma facing components. As regards impurity transport research, a number of working lines exploring several recently discovered effects have been developed: the effect of tangential drifts on stellarator neoclassical transport, the impurity flux driven by electric fields tangent to magnetic surfaces and attempts of experimental validation with Doppler reflectometry of the variation of the radial electric field on the flux surface. Concerning gyrokinetic simulations, two validation activities have been performed, the comparison with measurements of zonal flow relaxation in pellet-induced fast transients and the comparison with experimental poloidal variation of fluctuations amplitude. The impact of radial electric fields on turbulence spreading in the edge and scrape-off layer has been also experimentally characterized using a 2D Langmuir probe array. Another remarkable piece of work has been the investigation of the radial propagation of small temperature perturbations using transfer entropy. Research on the physics and modelling of plasma core fuelling with pellet and tracer-encapsulated solid-pellet injection has produced also relevant results. Neutral beam injection driven Alfvénic activity and its possible control by electron cyclotron current drive has been examined as well in TJ-II. Finally, recent results on alternative plasma facing components based on liquid metals are also presentedThis work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under Grant Agreement No. 633053. It has been partially funded by the Ministerio de Ciencia, Inovación y Universidades of Spain under projects ENE2013-48109-P, ENE2015-70142-P and FIS2017-88892-P. It has also received funds from the Spanish Government via mobility grant PRX17/00425. The authors thankfully acknowledge the computer resources at MareNostrum and the technical support provided by the Barcelona S.C. It has been supported as well by The Science and Technology Center in Ukraine (STCU), Project P-507F

NEK1 variants confer susceptibility to amyotrophic lateral sclerosis

To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research