Determining value in the treatment of activated PI3Kδ syndrome in Spain: a multicriteria decision analysis from the perspective of key stakeholders.

Introduction: Activated phosphoinositide 3-kinase (PI3K)δ syndrome (APDS) is an ultra-rare inborn error of immunity (IEI) combining immunodeficiency and immune dysregulation. This study determined what represents value in APDS in Spain from a multidisciplinary perspective applying multicriteria decision analysis (MCDA) methodology. Methods: A multidisciplinary committee of nine experts scored the evidence matrix. A specific framework for orphan drug evaluation in Spain and the weights assigned by a panel of 98 evaluators and decision-makers was used. Re-evaluation of scores was performed. Results: APDS is considered a very severe disease with important unmet needs, including misdiagnosis and diagnostic delay. Current management is limited to treatment of symptoms with off-label use of therapies supported by limited evidence. Therapeutic benefit is partial, resulting in limited disease control. Haematopoietic stem cell transplantation (HSCT), the only potential curative alternative, is restricted to a reduced patient population and without evidence of long-term efficacy or safety. All options present a limited safety profile. Data on patients' quality of life are lacking. APDS is associated with high pharmacological, medical and indirect costs. Conclusions: APDS is considered a severe disease, with limited understanding by key stakeholders of how treatment success is assessed in clinical practice, the serious impact that has on patients and the associated high economic burden. This study brings to light how MCDA methodology could represent a useful tool to complement current clinical and decision-making methods used by APDS experts and evaluators.

Barriers and drivers of public engagement in palliative care, Scoping review.

BACKGROUND: The integral model of Palliative Care recognizes the community as essential element in improving quality of life of patients and families. It is necessary to find a formula that allows the community to have a voice. The aim of this scoping review is to identify barriers and facilitators to engage community in PC. METHODS: Systematic search was conducted in NICE, Cochrane Library, Health Evidence, CINAHL and PubMed database. KEYWORDS: Palliative care, End of life care, community networks, community engagement, public engagement, community participation, social participation, barriers and facilitators. RESULTS: Nine hundred seventy-one results were obtained. Search strategy and inclusion criteria yielded 13 studies that were read in detail to identify factors influencing community engagement in palliative care, categorized into: Public health and public engagement; Community attitudes towards palliative care, death and preferences at the end of life; Importance of volunteers in public engagement programs; Compassionate communities. CONCLUSION: Societal awareness must be a facilitated process to catalyse public engagement efforts. National policy initiatives and regional system support provide legitimacy and focus is essential for funding. The first step is to get a sense of what is important to society, bearing in mind cultural differences and to channel those aspects through health care professionals; connecting the most assistential part with community resources. The process and long-term results need to be systematically evaluated.

Fibrosis avanzada asociada a esteatohepatitis no alcohólica (NASH) en España: resultados de un estudio Delphi / Advanced fibrosis associated with non-alcoholic steatohepatitis (NASH) in Spain: results of a Delphi study

Objetivo: Describir de manera detallada la epidemiología, diagnóstico, manejo clínico, opciones de tratamiento, impacto en la calidad de vida y necesidades no cubiertas de los pacientes con fibrosis hepática avanzada (F3-F4) asociada a esteatohepatitis no alcohólica (NASH) en España. Metodología: Estudio Delphi de dos rondas de consulta con 41 hepatólogos expertos de 16 comunidades autónomas para recoger su experiencia en práctica clínica. Resultados: La prevalencia estimada de pacientes adultos diagnosticados de fibrosis F3-F4 asociada a NASH en España es de 0,019% (intervalo de confianza [IC] 95%: 0,019-0,020%). Aproximadamente 7.588 adultos con este padecimiento están actualmente diagnosticados y son manejados en los Servicios de Aparato Digestivo de los hospitales españoles, y alrededor de 1.881 nuevos pacientes son diagnosticados cada año. El manejo es multidisciplinar e incluye las especialidades de Aparato Digestivo, Endocrinología y Medicina interna, considerando las frecuentes comorbilidades metabólicas asociadas (obesidad, diabetes mellitus tipo 2 o sobrecarga férrica dismetabólica). A pesar del claro impacto en la calidad de vida, este no se evalúa rutinariamente en la práctica clínica. Las técnicas diagnósticas no invasivas más utilizadas son la elastografía de transición y el índice de fibrosis hepática 4 (FIB-4). La ausencia de tratamientos eficaces y seguros se presenta como la principal necesidad no cubierta para el manejo de estos pacientes. Conclusiones: Este estudio proporciona una representación de la situación actual de los pacientes diagnosticados con fibrosis F3-F4 asociada a NASH en España, incrementando la evidencia disponible y contribuyendo a la toma de decisiones informadas por parte de los profesionales y el sistema sanitario. (AU)

Objective: To describe in detail the epidemiology, diagnosis, clinical management, treatment options, impact on quality of life and unmet needs of patients with advanced liver fibrosis (F3-F4) associated with non-alcoholic steatohepatitis (NASH) in Spain. Methodology: Delphi study of two rounds of consultation rounds with 41 expert hepatologists from 16 autonomous communities to collect their experience in clinical practice. Results: The estimated prevalence of adult patients diagnosed with F3-F4 fibrosis associated with NASH in Spain is 0.019% (95% confidence interval [CI]: 0.019-0.020%). Approximately 7,588 adults with this condition are currently diagnosed and managed in the Digestive System Services of Spanish hospitals, and around 1,881 new patients are diagnosed each year. Management is multidisciplinary and includes the specialties of Digestive System, Endocrinology and Internal Medicine, considering the frequently associated metabolic comorbidities (obesity, type 2 diabetes mellitus or dysmetabolic iron overload). Despite a clear impact on quality of life, this it is not routinely evaluated in clinical practice. The most widely used non-invasive diagnostic techniques are transitional elastography and liver fibrosis index 4 (FIB-4). The absence of effective and safe treatments appears as the main unmet need for the management of these patients. Conclusions: This study provides a representation of the current situation of patients diagnosed with F3-F4 fibrosis associated with NASH in Spain, increasing the evidence available and contributing to informed decision-making by professionals and the health system. (AU)

Computer Vision for Parkinson's Disease Evaluation: A Survey on Finger Tapping.

Parkinson's disease (PD) is a progressive neurodegenerative disorder whose prevalence has steadily been rising over the years. Specialist neurologists across the world assess and diagnose patients with PD, although the diagnostic process is time-consuming and various symptoms take years to appear, which means that the diagnosis is prone to human error. The partial automatization of PD assessment and diagnosis through computational processes has therefore been considered for some time. One well-known tool for PD assessment is finger tapping (FT), which can now be assessed through computer vision (CV). Artificial intelligence and related advances over recent decades, more specifically in the area of CV, have made it possible to develop computer systems that can help specialists assess and diagnose PD. The aim of this study is to review some advances related to CV techniques and FT so as to offer insight into future research lines that technological advances are now opening up.

Advanced fibrosis associated with non-alcoholic steatohepatitis (NASH) in Spain: results of a Delphi study. / Fibrosis avanzada asociada a esteatohepatitis no alcohólica (NASH) en España: resultados de un estudio Delphi.

OBJECTIVE: To describe in detail the epidemiology, diagnosis, clinical management, treatment options, impact on quality of life and unmet needs of patients with advanced liver fibrosis (F3-F4) associated with non-alcoholic steatohepatitis (NASH) in Spain. METHODOLOGY: Delphi study of two rounds of consultation rounds with 41 expert hepatologists from 16 autonomous communities to collect their experience in clinical practice. RESULTS: The estimated prevalence of adult patients diagnosed with F3-F4 fibrosis associated with NASH in Spain is 0.019% (95% confidence interval [CI]: 0.019-0.020%). Approximately 7,588 adults with this condition are currently diagnosed and managed in the Digestive System Services of Spanish hospitals, and around 1,881 new patients are diagnosed each year. Management is multidisciplinary and includes the specialties of Digestive System, Endocrinology and Internal Medicine, considering the frequently associated metabolic comorbidities (obesity, type 2 diabetes mellitus or dysmetabolic iron overload). Despite a clear impact on quality of life, this it is not routinely evaluated in clinical practice. The most widely used non-invasive diagnostic techniques are transitional elastography and liver fibrosis index 4 (FIB-4). The absence of effective and safe treatments appears as the main unmet need for the management of these patients. CONCLUSIONS: This study provides a representation of the current situation of patients diagnosed with F3-F4 fibrosis associated with NASH in Spain, increasing the evidence available and contributing to informed decision-making by professionals and the health system.

Value contribution of cenobamate for the treatment of Focal-Onset Seizures (FOS) in patients with drug-resistant epilepsy (DRE) in Spain through reflective Multi-Criteria Decision Analysis (MCDA).

INTRODUCTION: Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, despite the availability of many anti-seizure medications, including the latest options, called third-generation anti-seizure medications (ASMs), approximately 40% of people with epilepsy present drug-resistant epilepsy (DRE). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. In a chronic disease with a portfolio of available ASMs, the decision to introduce a new therapeutic alternative must follow a holistic evaluation of value provided. Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine the value contribution of a treatment in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. PURPOSE: The aim of this study was to determine the relative value contribution of cenobamate in the treatment of FOS in patients with DRE compared with third-generation ASMs using reflective MCDA-based methodology. METHODS: A systematic literature review (combining biomedical databases and grey literature sources) was performed to populate the Evidence and Value: Impact on DEcisionMaking (EVIDEM) MCDA framework adapted to determine what represents value in the management of FOS in patients with DRE in Spain. The study was conducted in two phases. The first took place in 2021 with a multi-stakeholder group of eight participants. The second phase was conducted in 2022 with a multi-stakeholder group of 32 participants. Participants were trained in MCDA methodology and scored four evidence matrices (cenobamate vs. brivaracetam, vs. perampanel, vs. lacosamide and vs. eslicarbazepine acetate). Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. RESULTS: DRE is considered a very severe condition associated with many important unmet needs, mainly with regard to the lack of more effective treatments to achieve the ultimate goal of treatment. Compared to third-generation ASMs, cenobamate is perceived to have a better efficacy profile based on improvements in responder rate and seizure freedom. Regarding safety, it is considered to have a similar profile to alternatives and a positive quality-of-life profile. Cenobamate results in lower direct medical costs (excluding pharmacological) and indirect costs. Overall, cenobamate is regarded as providing a high therapeutic impact and supported by high-quality evidence. CONCLUSIONS: Based on reflective MCDA methodology and stakeholders' experience in clinical management of epilepsy in Spain, cenobamate is perceived as a value-added option for the treatment of patients with DRE when compared with third-generation ASMs.

Deep learning and support vector machines for transcription start site identification.

Recognizing transcription start sites is key to gene identification. Several approaches have been employed in related problems such as detecting translation initiation sites or promoters, many of the most recent ones based on machine learning. Deep learning methods have been proven to be exceptionally effective for this task, but their use in transcription start site identification has not yet been explored in depth. Also, the very few existing works do not compare their methods to support vector machines (SVMs), the most established technique in this area of study, nor provide the curated dataset used in the study. The reduced amount of published papers in this specific problem could be explained by this lack of datasets. Given that both support vector machines and deep neural networks have been applied in related problems with remarkable results, we compared their performance in transcription start site predictions, concluding that SVMs are computationally much slower, and deep learning methods, specially long short-term memory neural networks (LSTMs), are best suited to work with sequences than SVMs. For such a purpose, we used the reference human genome GRCh38. Additionally, we studied two different aspects related to data processing: the proper way to generate training examples and the imbalanced nature of the data. Furthermore, the generalization performance of the models studied was also tested using the mouse genome, where the LSTM neural network stood out from the rest of the algorithms. To sum up, this article provides an analysis of the best architecture choices in transcription start site identification, as well as a method to generate transcription start site datasets including negative instances on any species available in Ensembl. We found that deep learning methods are better suited than SVMs to solve this problem, being more efficient and better adapted to long sequences and large amounts of data. We also create a transcription start site (TSS) dataset large enough to be used in deep learning experiments.

A human rights-based framework for qualitative dementia research.

BACKGROUND AND OBJECTIVES: People living with dementia have historically been excluded from qualitative research and their voices ignored due to the perception that a person with dementia is not able to express their opinions, preferences and feelings. Research institutions and organizations have contributed by adopting a paternalistic posture of overprotection. Furthermore, traditional research methods have proven to be exclusionary towards this group. The objective of this paper is to address the issue of inclusion of people with dementia in research and provide an evidence-based framework for dementia researchers based on the five principles of human rights: Participation, Accountability, Non-discrimination and equality, Empowerment and Legality (PANEL). DESIGN: This paper adapts the PANEL principles to the research context, and uses evidence from the literature to create a framework for qualitative research in people with dementia. This new framework aims to guide dementia researchers in designing studies around the needs of people with dementia, to improve involvement and participation, facilitate research development and maximize research outcomes. RESULTS: A checklist is presented with questions related to the five PANEL principles. These questions cover ethical, methodological and legal issues that researchers may need to consider while developing qualitative research for people with dementia. CONCLUSIONS: The proposed checklist offers a series of questions and considerations to facilitate the development of qualitative research in patients with dementia. It is inspired by current human rights work of recognized dementia researchers and organizations who have been directly involved in policy development. Future studies need to explore its utility in improving participation, facilitating ethics approvals and ensuring that outcomes are relevant to people with dementia.

A Low-Cost System Using a Big-Data Deep-Learning Framework for Assessing Physical Telerehabilitation: A Proof-of-Concept.

The consolidation of telerehabilitation for the treatment of many diseases over the last decades is a consequence of its cost-effective results and its ability to offer access to rehabilitation in remote areas. Telerehabilitation operates over a distance, so vulnerable patients are never exposed to unnecessary risks. Despite its low cost, the need for a professional to assess therapeutic exercises and proper corporal movements online should also be mentioned. The focus of this paper is on a telerehabilitation system for patients suffering from Parkinson's disease in remote villages and other less accessible locations. A full-stack is presented using big data frameworks that facilitate communication between the patient and the occupational therapist, the recording of each session, and real-time skeleton identification using artificial intelligence techniques. Big data technologies are used to process the numerous videos that are generated during the course of treating simultaneous patients. Moreover, the skeleton of each patient can be estimated using deep neural networks for automated evaluation of corporal exercises, which is of immense help to the therapists in charge of the treatment programs.

Number needed to treat and associated cost analysis of cenobamate versus third-generation anti-seizure medications for the treatment of focal-onset seizures in patients with drug-resistant epilepsy in Spain.

INTRODUCTION: Epilepsy is a serious neurological disease, ranking high in the top causes of disability. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, approximately 40% of patients suffer from Drug-Resistant Epilepsy (DRE) despite the availability of the latest options called third-generation Anti-Seizure Medications(ASMs). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. The introduction of a new drug increases the number of therapeutic options available, making it important to compare it with existing alternatives in terms of clinical benefit and efficiency. PURPOSE: This study aimed to compare the clinical benefit, in terms of the Number Needed to Treat (NNT), and the efficiency, in terms of Cost per NNT (CNT), associated with cenobamate versus third-generation ASMs used in Spain for the adjunctive treatment of FOS in patients with DRE. METHODS: The Number Needed to Treat data was calculated based on the ≥50% responder rate and seizure freedom endpoints (defined as the percentage of patients achieving 50% and 100% reduction in seizure frequency, respectively), obtained from pivotal clinical trials performed with cenobamate, brivaracetam, perampanel, lacosamide, and eslicarbazepine acetate. The NNT was established as the inverse of the treatment responder rate minus the placebo responder rate and was calculated based on the minimum, mid-range Daily Defined Dose (DDD), and maximum doses studied in the pivotal clinical trials of each ASM. CNT was calculated by multiplying the annual treatment cost by NNT values for each treatment option. RESULTS: In terms of NNT, cenobamate was the ASM associated with the lowest values at all doses for both ≥50% responder rate and seizure freedom compared with the alternatives. In terms of CNT, for ≥50% responder rate, cenobamate was the ASM associated with the lowest CNT values at DDD and lacosamide and eslicarbazepine acetate at the minimum and maximum dose, respectively. For seizure freedom, cenobamate was associated with the lowest CNT value at DDD and the maximum dose and lacosamide at the minimum dose. CONCLUSIONS: Cenobamate could represent the most effective ASM in all doses studied compared to the third-generation ASMs and the most efficient option at DDD for both ≥50% responder rate and seizure freedom. This study could represent an important contribution towards informed decision-making regarding the selection of the most appropriate therapy for FOS in adult patients with DRE from a clinical and economical perspective in Spain.

ODs with a positive TPR conclusion, not subject to a conditional approval, and approved without requering a pass would be more likely to be reimbursed in Spain.

BACKGROUND: The present study aims to assess clinical and regulatory variables that would influence pricing and reimbursement (P&R) decisions for Orphan Drugs (ODs) in Spain. ODs approved by the European Commission (EC) between 2006 and 2021 were classified according to their P&R status in Spain: approved, undergoing decision and rejected. A statistical analysis was carried out to assess the potential association between clinical and regulatory variables and P&R decision of ODs in Spain: therapeutic area, rarity of disease, existence of alternative therapies, availability of survival-related outcomes, safety profile, type of population, conditional approval status granted by the European Medicines Agency (EMA) and a positive Therapeutic Positioning Report (TPR) opinion. RESULTS: 111 ODs have been approved by the EC and have obtained marketing authorisation in Spain between 2006 and 2021. Out of the 111 ODs, 57 (51.4%) were reimbursed, 24 (21.6%) were undergoing decision and 30 (27%) were rejected. According to the statistical analysis, ODs with a positive TPR conclusion (p-value < 0.01), not subject to a conditional approval by the EMA (p-value < 0.05) and approved without the obligation to conduct a post-authorisation safety study (PASS) (p-value < 0.05), were statistically significant, and therefore, would be more likely to obtain P&R approval in Spain. CONCLUSIONS: This study shows that the TPR plays a key role in the P&R process in Spain and highlights that traditional evaluation tools, such us safety and efficacy, were the main drivers of P&R decisions for ODs. A positive conclusion of the TPR, non-conditional approval by the EMA and no obligation for a PASS seems to favourably affect P&R decisions in Spain.

Determining What Represents Value in the Treatment of Refractory or Unexplained Chronic Cough from the Perspective of Key Stakeholders in Spain Using Multi-Criteria Decision Analysis.

BACKGROUND AND OBJECTIVE: Chronic cough is defined as cough lasting for more than 8 weeks. It can be described as refractory when persisting despite thorough clinical assessment and treatment of any cough-related underlying condition, or unexplained when no underlying cough-related condition can be identified. Refractory or unexplained chronic cough (RCC|UCC) greatly affects patient health-related quality of life (HRQoL). Although around 10% of the population suffer from chronic cough (with 40-60% of these patients suffering from RCC|UCC), there is limited information available in the literature about the condition and the assessment of treatment success. This study aimed to determine what represents value in the treatment of RCC|UCC from the perspective of key stakeholders in Spain using Multi-Criteria Decision Analysis (MCDA) methodology. METHODS: A literature review was conducted to adapt the MCDA framework to the specific context of RCC|UCC. A total of 24 participants were involved, representing three key stakeholder groups (7 patients, 9 physicians and 8 hospital pharmacists). The study was structured in two phases. In Phase 1, participants validated the adapted MCDA framework and assigned relative weights (100-point allocation) to the framework's value criteria/sub-criteria during three individual stakeholder meetings, one per each stakeholder group. In Phase 2, participants were brought together in a multi-stakeholder meeting to review findings of each stakeholder group, after which stakeholders repeated the weighting exercise as a collective group. All meetings included reflective discussion by participants of each value criteria/sub-criteria included within the adapted MCDA framework, where stakeholders shared their perspectives and opinions on what represents value in RCC|UCC. RESULTS: Refractory or unexplained chronic cough is regarded as a chronic medical condition, with variable severity across patients and the potential to heavily impact their HRQoL (including physical, psychological and social/work productivity domains). Current treatments used by healthcare professionals, which have not been specifically developed and are not approved for RCC|UCC, show limited clinical effectiveness and associated safety and tolerability issues, which result in frequent treatment discontinuations. The reduction of the average cough frequency over a 24-h period is regarded as the primary goal of treatment by stakeholders, with the aim of improving HRQoL. Improvement of other cough symptoms, such as intensity, is also considered important. Minor adverse events and a slower onset of treatment effect would be acceptable to stakeholders if accompanied by strong efficacy and improvement in HRQoL. Given the inability to measure cough frequency in clinical practice, Patient-Reported Outcomes (PROs) could be considered a proxy of treatment effectiveness. A multidisciplinary approach to the condition is regarded as key for treatment success. CONCLUSIONS: Refractory or unexplained chronic cough is a medical condition that seriously impacts patients' HRQoL. The primary goal of treatment is to improve patients' HRQoL by reducing the frequency and intensity of cough.

Determination of the economically justifiable price of cenobamate in the treatment of focal-onset seizures in adult patients with drug-resistant epilepsy in Spain.

OBJECTIVE: To determine the economically justifiable price (EJP) of cenobamate to become a cost-effective alternative compared with third-generation anti-seizure medications in the treatment of focal-onset seizures (FOS) in adult patients with drug-resistant epilepsy (DRE) in Spain. METHODS: Cost-effectiveness analysis compared cenobamate with brivaracetam, perampanel, eslicarbazepine acetate, and lacosamide. Markov model simulation of treatment pathway over a 60-year time horizon is presented. We determined the effectiveness and quality-adjusted life-years (QALYs) of health status and disutilities associated with treatment-related adverse events. Acquisition costs and use of medical resources were obtained from published literature and expert opinion. Base-case of cenobamate's EJP calculated applying a willingness-to-pay (WTP) threshold of €21,000/QALY. Analyses were performed at different thresholds, including dominant price scenario. Result robustness was assessed through sensitivity analyses. RESULTS: Base-case shows that cenobamate's daily EJP of €7.30 is cost-effective for a threshold of €21,000/QALY. At a daily price of €5.45, cenobamate becomes dominant over all treatment alternatives producing cost-savings for the national health system (NHS). Sensitivity analyses supported the robustness of base-case findings. CONCLUSIONS: Treatment with cenobamate produces incremental clinical benefit over third-generation ASMs, and at the base-case, EJP could represent a cost-effective option for the adjunctive treatment of FOS in adult patients with DRE in Spain.

The contribution of fenfluramine to the treatment of Dravet syndrome in Spain through Multi-Criteria Decision Analysis.

INTRODUCTION: Dravet Syndrome (DS) is a severe, developmental epileptic encephalopathy (DEE) that begins in infancy and is characterized by pharmaco-resistant epilepsy and neurodevelopmental delay. Despite available antiseizure medications (ASMs), there is a need for new therapeutic options with greater efficacy in reducing seizure frequency and with adequate safety and tolerability profiles. Fenfluramine is a new ASM for the treatment of seizures associated with DS as add-on therapy to other ASMs for patients aged 2 years and older. Fenfluramine decreases seizure frequency, prolongs periods of seizure freedom potentially helping to reduce risk of Sudden Unexpected Death in Epilepsy (SUDEP) and improves patient cognitive abilities positively impacting on patients' Quality of Life (QoL). Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine what represents value in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. The aim of this study was to determine the relative value contribution of fenfluramine for the treatment of DS in Spain using MCDA. METHOD: A literature review was performed to populate an adapted a MCDA framework for orphan-drug evaluation in Spain. A panel of ten Spanish experts, including neurologists, hospital pharmacists, patient representatives and decision-makers, scored four comparative evidence matrices. Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. RESULTS: Dravet syndrome is considered a severe, rare disease with significant unmet needs. Fenfluramine is perceived to have a higher efficacy profile than all available alternatives, with a better safety profile than stiripentol and topiramate and to provide improved QoL versus studied alternatives. Fenfluramine results in lower other medical costs in comparison with stiripentol and clobazam. Participants perceived that fenfluramine could lead to indirect costs savings compared to available alternatives due to its efficacy in controlling seizures. Overall, fenfluramine's therapeutic impact on patients with DS is considered high and supported by high-quality evidence. CONCLUSIONS: Based on reflective MCDA, fenfluramine is considered to add greater benefit in terms of efficacy, safety and QoL when compared with available ASMs.

Translation to Spanish and validation of a scale for the observation of breastfeeding: The Bristol Breastfeeding Assessment Tool.

INTRODUCTION: The observation of a feeding by a professional is important to strengthen breastfeeding. The Bristol Breastfeeding Assessment Tool (BBAT) was translated into Spanish and validated. MATERIAL AND METHODS: Translation and back-translation of the original scale was done. Six pediatricians and six pediatric nurses collaborated. At the newborn's first visit, a feeding was observed and the pediatrician and nurse scored the BBAT scale independently. The nurse also scored the LATCH Breastfeeding Assessment (LATCH) and each mother filled out the Breastfeeding Self-Efficacy Scale (BSES-SF). Mothers were appointed a week later and the nurse re-scored the BBAT. RESULTS: A total of 62 mothers participated. There was good internal consisitency for the BBAT (Cronbach's alpha = 0.83 in the assessment made by the nurses and Cronbach's alpha = 0.79 in the assessment made by the pediatricians). Inter-rater consistency showed an intra-class correlation coefficient of 0.91, while for the test-retest was 0.67. Concurrent validity with the BSES-SF scale was good and with the LATCH scale very good. The factor analysis showed the one-dimensional character of the scale and a good homogeneity of the 4 items (positioning = 0.771, attachment = 0.852, sucking = 0.856 and swallowing = 0.679). CONCLUSIONS: The scale obtained in Spanish shows good reliability and validity. The BBAT is an easy-to-use tool that allows breastfeeding assessment and determines the aspects that need to be improved.

Identifying key unmet needs and value drivers in the treatment of focal-onset seizures (FOS) in patients with drug-resistant epilepsy (DRE) in Spain through Multi-Criteria Decision Analysis (MCDA).

INTRODUCTION: Epilepsy is a serious neurological disease, ranking high in the top causes of disability. Approximately 40% of patients with epilepsy are pharmacoresistant after their seizures failed at least two antiseizure medications (ASMs). Adult patients experiencing focal-onset seizures (FOS) account for approximately 60% of all patients with epilepsy and they are more likely to become drug-resistant epilepsy (DRE) than those with generalized onset. Drug-resistant epilepsy is associated with mortality, morbidity, and reduced quality of life. The information available on the clinical management, health outcomes, and unmet needs of the disease within the Spanish healthcare environment is very limited. Multi-Criteria Decision Analysis (MCDA) allows determination of what represents value in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner and from the perspective of relevant stakeholders. PURPOSE: The aim of this study was to identify the burden of DRE (clinical, quality of life, and economic) and the unmet needs in Spain and to determine what represents value in the treatment of FOS in DRE patients from the perspective of Spanish epileptologists. METHODS: The steps taken to carry out the MCDA were based on previously published good methodological practices. A systematic literature review (combining biomedical databases and gray literature sources) was performed between March and April 2020. Results were reviewed and validated with three epileptologists in June 2020 and used to develop a MCDA value framework, adapted for FOS in DRE, composed of 12 quantitative criteria and 3 contextual criteria. A group of six Spanish epileptologists from four Spanish regions were trained in MCDA methodology before individually validating value criteria (and their definitions based on literature review findings) and assigned relative weights using an ordinal 6-points scale. Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. RESULTS: Drug-resistant epilepsy is considered a very severe health problem with important unmet needs affecting a considerably sized population. While safety and impact on quality of life of available ASMs are considered adequate, efficacy remains insufficient for patients to achieve seizure freedom and maintain it over time. Hence, the therapeutic benefit of pharmacological treatments currently used is regarded as suboptimal. Drug-resistant epilepsy management is associated with moderate pharmacological, relevant direct medical and high indirect costs. Quality of evidence available for current treatments is moderate. It is considered that DRE does not currently stand as a key priority for the Spanish healthcare system. CONCLUSIONS: Drug-resistant epilepsy is considered a very severe health problem associated with relevant unmet needs. These include the lack of availability of specific treatment protocols, the need to improve early diagnosis by increasing the number of referrals to specialized epilepsy units and the availability of specific ASMs with improved efficacy and safety profiles, allowing to reach treatment objectives. Reflective MCDA provided a standardized, transparent approach to evaluate multiple criteria ascertaining what represents value from a holistic point of view and from the perspective of clinical experts, facilitating decision-making.

[Translation to Spanish and validation of a scale for the observation of breastfeeding: The Bristol Breastfeeding Assessment Tool]. / Traducción al español y validación de una escala para la observación de una toma de lactancia materna: la «Bristol Breastfeeding Assessment Tool¼.

INTRODUCTION: The observation of a feeding by a professional is important to strengthen breastfeeding. The Bristol Breastfeeding Assessment Tool (BBAT) was translated into Spanish and validated. MATERIAL AND METHODS: Translation and back-translation of the original scale was done. Six pediatricians and six pediatric nurses collaborated. At the newborn's first visit, a feeding was observed and the pediatrician and nurse scored the BBAT scale independently. The nurse also scored the LATCH Breastfeeding Assessment (LATCH) and each mother filled out the Breastfeeding Self-Efficacy Scale (BSES-SF). Mothers were appointed a week later and the nurse re-scored the BBAT. RESULTS: A total of 62 mothers participated. There was good internal consistency for the BBAT (Cronbach's alpha = 0.83 in the assessment made by the nurses and Cronbach's alpha = 0.79 in the assessment made by the pediatricians). Inter-rater consistency showed an intra-class correlation coefficient of 0.91, while for the test-retest was 0.67. Concurrent validity with the BSES-SF scale was good and with the LATCH scale very good. The factor analysis showed the one-dimensional character of the scale and a good homogeneity of the 4 items (positioning = 0.771, attachment = 0.852, sucking = 0.856 and swallowing = 0.679). CONCLUSIONS: The scale obtained in Spanish shows good reliability and validity. The BBAT is an easy-to-use tool that allows breastfeeding assessment and determines the aspects that need to be improved.

Management of chronic liver disease-associated severe thrombocytopenia in Spain: a view from the experts

BACKGROUND: chronic liver disease (CLD) patients often present thrombocytopenia (TCP) and when severe, it may prevent them from undergoing necessary invasive procedures due to an increased bleeding risk. The lack of scientific evidence makes it impossible to determine key aspects of the current management and associated healthcare burden of these patients in Spain. PURPOSE: to gain insight into the current situation of patients with CLD-associated severe TCP undergoing invasive procedures in Spain, based on the experience of clinical experts. METHODS: national Delphi study involving 32 medical experts. RESULTS: the estimated prevalence of CLD-associated severe TCP is approximately 5,967, with an annual incidence of 1,148 new patients. Patients undergo a median of 1 (0-3) invasive procedures/year. Platelet transfusions (PTs) are the standard option to raise platelet counts and are associated with significant burden. The achievement of target platelet levels (≥ 50 X 109/l) after a transfusion is not routinely measured. The lack of effectiveness and short life span of transfused platelets can lead to procedure cancellations and bleeding events, which potentially affect patient outcomes. Adverse events occur in 1-25 % of patients, including mild (febrile and allergic reactions) and severe events (e.g., transfusion-related acute lung injury). Between 5-15 % of patients are unfit to receive PTs and approximately 3 % are treated off-label with thrombopoietin receptor agonists. CONCLUSIONS: this study provides a snapshot of the current situation in Spain, highlighting that the current management is poorly standardized and suboptimal in some cases. The results suggest the benefit of developing a consensus document to address some of these shortcomings and to advance in the search for alternatives to PTs

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