Exploring the Molecular Aspects of Myeloproliferative Neoplasms Associated with Unusual Site Vein Thrombosis: Review of the Literature and Latest Insights.

Myeloproliferative neoplasms (MPNs) are the leading causes of unusual site thrombosis, affecting nearly 40% of individuals with conditions like Budd-Chiari syndrome or portal vein thrombosis. Diagnosing MPNs in these cases is challenging because common indicators, such as spleen enlargement and elevated blood cell counts, can be obscured by portal hypertension or bleeding issues. Recent advancements in diagnostic tools have enhanced the accuracy of MPN diagnosis and classification. While bone marrow biopsies remain significant diagnostic criteria, molecular markers now play a pivotal role in both diagnosis and prognosis assessment. Hence, it is essential to initiate the diagnostic process for splanchnic vein thrombosis with a JAK2 V617F mutation screening, but a comprehensive approach is necessary. A multidisciplinary strategy is vital to accurately determine the specific subtype of MPNs, recommend additional tests, and propose the most effective treatment plan. Establishing specialized care pathways for patients with splanchnic vein thrombosis and underlying MPNs is crucial to tailor management approaches that reduce the risk of hematological outcomes and hepatic complications.

Health equity, care access and quality in headache - part 1.

Current definitions of migraine that are based mainly on clinical characteristics do not account for other patient's features such as those related to an impaired quality of life, due to loss of social life and productivity, and the differences related to the geographical distribution of the disease and cultural misconceptions which tend to underestimate migraine as a psychosocial rather than neurobiological disorder.Global differences definition, care access, and health equity for headache disorders, especially migraine are reported in this paper from a collaborative group of the editorial board members of the Journal of Headache and Pain. Other components that affect patients with migraine, in addition to the impact promoted by the migraine symptoms such as stigma and social determinants, are also reported.

The World Health Organization Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders and the headache revolution: from headache burden to a global action plan for headache disorders.

The World Health Organization (WHO) Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders was developed by WHO to address the worldwide challenges and gaps in provision of care and services for people with epilepsy and other neurological disorders and to ensure a comprehensive, coordinated response across sectors to the burden of neurologic diseases and to promote brain health across life-course. Headache disorders constitute the second most burdensome of all neurological diseases after stroke, but the first if young and midlife adults are taken into account. Despite the availability of a range of treatments, disability associated with headache disorders, and with migraine, remains very high. In addition, there are inequalities between high-income and low and middle income countries in access to medical care. In line with several brain health initiatives following the WHOiGAP resolution, herein we tailor the main pillars of the action plan to headache disorders: (1) raising policy prioritization and strengthen governance; (2) providing effective, timely and responsive diagnosis, treatment and care; (3) implementing strategies for promotion and prevention; (4) fostering research and innovation and strengthen information systems. Specific targets for future policy actions are proposed. The Global Action Plan triggered a revolution in neurology, not only by increasing public awareness of brain disorders and brain health but also by boosting the number of neurologists in training, raising research funding and making neurology a public health priority for policy makers. Reducing the burden of headache disorders will not only improve the quality of life and wellbeing of people with headache but also reduce the burden of neurological disorders increasing global brain health and, thus, global population health.

Rethinking headache as a global public health case model for reaching the SDG 3 HEALTH by 2030.

The 2030 Agenda for Sustainable Development sets out, through 17 Sustainable Development Goals (SDGs), a path for the prosperity of people and the planet. SDG 3 in particular aims to ensure healthy lives and promote well-being for all at all ages and includes several targets to enhance health. This review presents a "headache-tailored" perspective on how to achieve SDG 3 by focusing on six specific actions: targeting chronic headaches; reducing the overuse of acute pain-relieving medications; promoting the education of healthcare professionals; granting access to medication in low- and middle-income countries (LMIC); implementing training and educational opportunities for healthcare professionals in low and middle income countries; building a global alliance against headache disorders. Addressing the burden of headache disorders directly impacts on populations' health, as well as on the possibility to improve the productivity of people aged below 50, women in particular. Our analysis pointed out several elements, and included: moving forward from frequency-based parameters to define headache severity; recognizing and managing comorbid diseases and risk factors; implementing a disease management multi-modal management model that incorporates pharmacological and non-pharmacological treatments; early recognizing and managing the overuse of acute pain-relieving medications; promoting undergraduate, postgraduate, and continuing medical education of healthcare professionals with specific training on headache; and promoting a culture that favors the recognition of headaches as diseases with a neurobiological basis, where this is not yet recognized. Making headache care more sustainable is an achievable objective, which will require multi-stakeholder collaborations across all sectors of society, both health-related and not health-related. Robust investments will be needed; however, considering the high prevalence of headache disorders and the associated disability, these investments will surely improve multiple health outcomes and lift development and well-being globally.

Epidemiology of cutaneous T-cell lymphomas: state of the art and a focus on the Italian Marche region.

Among primary cutaneous T-cell lymphomas (CTCL), mycosis fungoides (MF) is the most frequent and, along with Sézary syndrome (SS), the best-studied subtype. Most available studies on epidemiology of MF and SS are based on small cohorts or different inclusion criteria. Moreover, although this has become a hot topic, most studies show limitations, such as selection bias and lack of clinical information or follow-up data. Therefore, no reliable conclusions can be drawn. This paper reviews the current data underpinning our understanding of the epidemiology of MF and SS, and presents some original findings based on data retrieved from the cutaneous lymphoma registry of the Italian Marche region. The Marche Regional Cutaneous Lymphoma Registry is a multidisciplinary team founded 27 years ago to share the management of these rare disorders. All patients with a clinical and histologically confirmed diagnosis of primary cutaneous lymphoma are centralized in Ancona (Italy) at the Haematology Clinic, Polytechnic University of Marche, for clinical evaluation, staging, treatment, and follow-up. This paper emphasizes the need for a national registry of pCLs in Italy, as no detailed epidemiological information is available in the country except for the Marche Regional Cutaneous Lymphoma Registry. A national registry would allow for more comprehensive data collection from all over Italy and could provide more accurate information on incidence and epidemiology. This would be beneficial for understanding the pathogenesis and diagnostic procedures of these diseases and could improve patient outcomes. Therefore, we advise the creation of a national registry of pCLs in Italy.

Recomendaciones de “no hacer” en la consulta de Atención Primaria / Recommendations for “not to do” in primary care practice

Introducción: en los últimos años se ha observado un exceso de prácticas clínicas innecesarias en Pediatría que carecen de suficiente evidencia científica y generan costos significativos, además de resultar molestas para el paciente y no aportar beneficios adicionales. Por ello, diversas sociedades e instituciones científicas han propuesto recomendaciones para evitar estas intervenciones ineficaces y científicamente injustificadas. Material y métodos: el proyecto fue coordinado por el grupo de trabajo PrevInfad de la Asociación Española de Pediatría de Atención Primaria (AEPap). Se desarrolló en dos fases a través del intercambio de correos electrónicos. En la primera, se solicitó a los coordinadores que divulgaran el proyecto y recopilaran propuestas de intervenciones innecesarias. En la segunda, se realizó la selección de las recomendaciones mediante el método Delphi y dos rondas de votación. Resultados: en la primera fase se obtuvieron 40 propuestas de recomendaciones de “no hacer”. En la primera ronda de la segunda fase se aceptaron 7 propuestas. Cinco recomendaciones fueron rechazadas y 28 fueron consideradas dudosas y pasaron a una segunda valoración. En la segunda ronda se aceptó una recomendación adicional. En total, se aprobaron 8 recomendaciones de “no hacer”. Conclusiones: la AEPap elaboró una lista de recomendaciones de “no hacer” en Pediatría en colaboración con sus grupos de trabajo y asociaciones federadas utilizando la metodología Delphi para el consenso entre expertos. Estas recomendaciones buscan mejorar la calidad asistencial y promover la utilización adecuada de recursos en la Atención Primaria pediátrica (AU)

Introduction: in recent years, there has been an excess of unnecessary clinical practices in pediatrics that lack sufficient scientific evidence and generate significant costs, in addition to being bothersome and not providing additional benefits. For this reason, various scientific societies and institutions have proposed recommendations to avoid these ineffective and scientifically unjustified interventions.Material and methods: the project was coordinated by the PrevInfad working group of the Spanish Association of Primary Care Pediatrics (AEPap). It was developed in two phases through the exchange of e-mails. In the first phase, the coordinators were asked to disseminate the project and to collect proposals for unnecessary interventions. In the second phase, the recommendations were selected using the Delphi method and two rounds of voting.Results: in the first phase, 40 proposals for 'do not do' recommendations were obtained. In the first round of the second phase, seven proposals were accepted. Five recommendations were rejected and 28 were considered doubtful and passed to a second assessment. One additional recommendation was accepted in the second round. In total, 8 'do not do' recommendations were approved.Conclusions: the AEPap developed a list of 'do not do' recommendations in pediatrics in collaboration with its working groups and federated associations using the Delphi methodology for consensus among experts. These recommendations aim to improve the quality of care and promote the appropriate use of resources in pediatric primary care. (AU)

Who cares about migraine? Pathways and hurdles in the European region - access to care III.

BACKGROUND: Migraine is a highly prevalent primary headache disorder and a leading cause of disability. Difficulties in access to care during diagnostic and therapeutic journey contribute to the disease burden. Several target-specific drugs have reached the market in the past four years and have modified the treatment paradigm in migraine. The aim of this study is to provide an updated snapshot of the pathways and hurdles to care for migraine in different European countries by directly asking patients. METHODS: In 2021 the European Migraine and Headache Alliance proposed a 39-item questionnaire that was administered online to an adult migraine population in European countries. Questions were focused on socio-demographic and migraine data, access to diagnosis and treatment, disease-related burden and the main channel for disease information. RESULTS: A total of 3169 questionnaires were returned from 10 European countries. Responders were predominantly females, age range 25-59 years, with a migraine history longer than 10 years in 82% of cases, and with at least 8 headache days per month in 57% of cases. Respondents reported limitations in social, working and personal life during both the ictal and interictal phase. The activities mostly impaired during the attacks were driving (55%), cooking or eating (42%), taking care of family/childcare (40%) and getting medicines at the pharmacy (40%). The most frequently reported unmet need was the long delay between the first visit and migraine diagnosis: 34% of respondents had to see ≥ 4 specialists before being correctly diagnosed, and between the diagnosis and treatment prescription: > 5 years in 40% of cases. The most relevant needs in terms of quality of life were the desire for a lower migraine frequency, an effective treatment and a greater involvement in society. CONCLUSIONS: Data from the present survey point to the existence and persistence of multiple hurdles that result in significant limitations to access to care and to the patients' social life. A close cooperation between decision makers, healthcare workers and patients is needed to overcome these barriers.

A Journey Through JAK Inhibitors for the Treatment of Myeloproliferative Diseases.

PURPOSE OF REVIEW: Chronic myeloproliferative neoplasms (MPN) represent a group of diseases characterised by constitutive activation of the JAK/STAT pathway in a clonal myeloid precursor. The therapeutic approach aims to treat the symptom burden (headache, itching, debilitation), splenomegaly, slow down the fibrotic proliferation in the bone marrow and reduce the risk of thrombosis/bleeding whilst avoiding leukaemic transformation. RECENT FINDINGS: In recent years, the advent of JAK inhibitors (JAKi) has significantly broadened treatment options for these patients. In myelofibrosis, symptom control and splenomegaly reduction can improve quality of life with improved overall survival, not impacting progression into acute leukaemia. Several JAKi are available and used worldwide, and combination approaches are now being explored. In this chapter, we review the approved JAKi, highlighting its strengths, exploring potential guidelines in choosing which one to use and reasoning towards future perspectives, where the combinations of therapies seem to promise the best results.

Social Media Listening and Digital Profiling Study of People With Headache and Migraine: Retrospective Infodemiology Study.

BACKGROUND: There is an unmet need for a better understanding and management of headache, particularly migraine, beyond specialist centers, which may be facilitated using digital technology. OBJECTIVE: The objective of this study was to identify where, when, and how people with headache and migraine describe their symptoms and the nonpharmaceutical and medicinal treatments used as indicated on social media. METHODS: Social media sources, including Twitter, web-based forums, blogs, YouTube, and review sites, were searched using a predefined search string related to headache and migraine. The real-time data from social media posts were collected retrospectively for a 1-year period from January 1, 2018, to December 31, 2018 (Japan), or a 2-year period from January 1, 2017, to December 31, 2018 (Germany and France). The data were analyzed after collection, using content analysis and audience profiling. RESULTS: A total of 3,509,828 social media posts related to headache and migraine were obtained from Japan in 1 year and 146,257 and 306,787 posts from Germany and France, respectively, in 2 years. Among social media sites, Twitter was the most used platform across these countries. Japanese sufferers used specific terminology, such as "tension headaches" or "cluster headaches" (36%), whereas French sufferers even mentioned specific migraine types, such as ocular (7%) and aura (2%). The most detailed posts on headache or migraine were from Germany. The French sufferers explicitly mentioned "headache or migraine attacks" in the "evening (41%) or morning (38%)," whereas Japanese mentioned "morning (48%) or night (27%)" and German sufferers mentioned "evening (22%) or night (41%)." The use of "generic terms" such as medicine, tablet, and pill were prevalent. The most discussed drugs were ibuprofen and naproxen combination (43%) in Japan; ibuprofen (29%) in Germany; and acetylsalicylic acid, paracetamol, and caffeine combination (75%) in France. The top 3 nonpharmaceutical treatments are hydration, caffeinated beverages, and relaxation methods. Of the sufferers, 44% were between 18 and 24 years of age. CONCLUSIONS: In this digital era, social media listening studies present an opportunity to provide unguided, self-reported, sufferers' perceptions in the real world. The generation of social media evidence requires appropriate methodology to translate data into scientific information and relevant medical insights. This social media listening study showed country-specific differences in headache and migraine symptoms experienced and in the times of the day and treatments used. Furthermore, this study highlighted the prevalence of social media usage by younger sufferers compared to that by older sufferers.

Satisfaction outcomes for patients and physicians following use of a new hyaluronic acid fillers.

BACKGROUND: The aesthetic appearance of the skin, with the emergence of wrinkles, blemishes, and infraorbital hollowing, can be a cause of social distress and is a process exacerbated by aging. The presence of skin imperfections and aging is partly due to a loss of hyaluronic acid (HA), which normally contributes to a maintain a healthy and voluminous skin. Attempts to restore volume and revert the signs of aging have therefore focused on the use of dermatologic fillers based on HA. AIM: Here, we tested the safety and efficacy of MelHA®-Monophasic Elastic Hyaluronic Acid (Concilium FEEL® filler products) containing HA at different concentrations and injected at different sites according to recommendations. METHODS: Five different physicians assessed 42 patients across five different medical facilities in Italy, where they performed the treatment and assessed the patients after a follow-up visit. Safety and efficacy of the treatment and change in quality of life after treatment were evaluated with two surveys, one directed to medical personnel, and one directed to patients. RESULTS: Our results show that, across all products and personalized treatments, patients', physicians' and "independent photography reviewer" satisfaction was very high and that the treatment show a favorable safety profile. CONCLUSION: These results are promising and suggest the use of Concilium Feel® filler products can contribute to an increased self-esteem and quality of life in aging patients.

The Migraine Stigma Kaleidoscope View.

The stigma of migraine, despite an impressive body of data on the epidemiological of migraine and the associated disability, burden and cost of migraine to patients, has not been fully evaluated as an important factor in the chronicization of the disease and social isolation of the patient. In this commentary, we present three points of view. From the point of view of a European advocacy body active in the field of migraine medicine, actions to improve the perception of migraine within the community regarding the stigma for people with migraine are presented at the personal, relational and occupational levels. From the point of view of a clinician who is an expert on migraine, proposals are made for treatment and rehabilitation paths specifically dedicated to the reintegration of these individuals into social contexts.

Lipidation and PEGylation Strategies to Prolong the in Vivo Half-Life of a Nanomolar EphA4 Receptor Antagonist.

The EphA4 receptor tyrosine kinase plays a role in neurodegenerative diseases, inhibition of nerve regeneration, cancer progression and other diseases. Therefore, EphA4 inhibition has potential therapeutic value. Selective EphA4 kinase inhibitors are not available, but we identified peptide antagonists that inhibit ephrin ligand binding to EphA4 with high specificity. One of these peptides is the cyclic APY-d3 (ßAPYCVYRßASWSC-NH2), which inhibits ephrin-A5 ligand binding to EphA4 with low nanomolar binding affinity and is highly protease resistant. Here we describe modifications of APY-d3 that yield two different key derivatives with greatly increased half-lives in the mouse circulation, the lipidated APY-d3-laur8 and the PEGylated APY-d3-PEG4. These two derivatives inhibit ligand induced EphA4 activation in cells with sub-micromolar potency. Since they retain high potency and specificity for EphA4, lipidated and PEGylated APY-d3 derivatives represent new tools for discriminating EphA4 activities in vivo and for preclinical testing of EphA4 inhibition in animal disease models.

Opciones terapéuticas para la retirada de “superpegamentos” de la piel / Therapeutic options for removing superglues from the skin

El cianocrilato es un compuesto adhesivo que se utiliza en la fabricación de “superpegamentos”. En contacto con tejidos de algodón o lana puede producir quemaduras térmicas. Por el contrario, en contacto sobre piel sana se han descrito dermatitis de contacto o alérgica pero no quemaduras. Caso clínico. Niña de 8 años que acude a urgencias tras haber derramado de manera accidental un “superpegamento” directamente sobre una mano y ambas extremidades inferiores, permaneciendo con el pegamento en contacto con la piel durante 3 horas sin poder retirarlo en domicilio. En la exploración destacaba gran eritema en varias regiones subyacentes al pegamento, sin ampollas, heridas ni sangrado. El pegamento se retiró bajo sedoanalgesia con lavavajillas líquido diluido en agua tibia, sin apreciarse solución de continuidad ni quemadura. Conclusiones. Existen numerosas medidas para la retirada de adhesivos de la piel. Escoger la opción terapéutica viene determinado, entre otros factores, por la presencia de lesiones cutáneas bajo el adhesivo. La aplicación de acetona está contraindicada en pieles con lesiones debido a que puede empeorar la irritación de las mismas. La demora hasta la retirada del adhesivo puede influir en el éxito del tratamiento; así como en la aparición de posibles secuelas (AU)

Cyanoacrylate is an adhesive used as a component in most of “super glues”. It can cause thermal burns if in contact with wool or cotton fabric. Nevertheless, in contact with intact skin it can cause contact or allergic dermatitis, but no thermal burns have been described.Clinical case: 8-year-old girl who had suffered an accidental fall of one of these glues directly on one of her hands and both lower extremities, and who had remained with the glue in contact with the skin for 3 hours. On examination we observed erythema on several regions underlying the glue, without blisters, wounds or bleeding. The glue was removed with warm water and detergent. No open wounds or burns were noticed.Conclusions: There are different ways to remove adhesives from the skin. Choosing the correct therapeutic option is determined, among other factors, by the presence of skin lesions under the adhesive. The use of acetone is contraindicated in injured skin because it can worsen the irritation. The delay in the removal of the adhesive can influence the success of the treatment and the type of treatment to be applied. (AU)

Prognosis in early stage cutaneous T-cell lymphoma treated with psoralen plus ultraviolet A irradiation and low-dose interferon-α: Long-term efficacy and survival according to conventional and emerging clinical endpoints.

Patients with early stage cutaneous T cell lymphoma (CTCL) usually have a benign and chronic disease course, characterized by temporally response to conventional skin directed therapies and intrinsic possibility to evolve. Using the combination of psoralen plus ultraviolet A irradiation (PUVA) and low-dose interferon-α (INF), the principal treatment goal is to keep confined the disease to the skin, preventing disease progression. Among 87 patients with early stage IA to IIA MF treated with low-dose IFN-α2b and PUVA in our center, complete remission (CR) were reported in 70 patients (80.5%) and the overall response rate (ORR) was 97.8% (n = 85), with a median time to best response to therapy of 5 months (range, 1-30). Among the responders, only the 8% of patients had a relapse with major event. The median follow-up was 207 months (range, 6-295). Survival data showed a median overall survival (OS) not reached (95% CI; 235-NR months), a disease free survival (DFS) of 210 months (95% CI; 200-226 months) and a median time to next treatment (TTNT) of 38.5 months (95% CI, 33-46 months). The long follow up of this study verifies our preliminary results already published in 2006 and confirms the efficacy of INF-PUVA combination therapy in a real world setting, according conventional (OS and DFS) and emerging (TTNT) clinical endpoint of treatment efficacy.

Molecular Pathogenesis of Myeloproliferative Neoplasms: From Molecular Landscape to Therapeutic Implications.

Despite distinct clinical entities, the myeloproliferative neoplasms (MPN) share morphological similarities, propensity to thrombotic events and leukemic evolution, and a complex molecular pathogenesis. Well-known driver mutations, JAK2, MPL and CALR, determining constitutive activation of JAK-STAT signaling pathway are the hallmark of MPN pathogenesis. Recent data in MPN patients identified the presence of co-occurrence somatic mutations associated with epigenetic regulation, messenger RNA splicing, transcriptional mechanism, signal transduction, and DNA repair mechanism. The integration of genetic information within clinical setting is already improving patient management in terms of disease monitoring and prognostic information on disease progression. Even the current therapeutic approaches are limited in disease-modifying activity, the expanding insight into the genetic basis of MPN poses novel candidates for targeted therapeutic approaches. This review aims to explore the molecular landscape of MPN, providing a comprehensive overview of the role of drive mutations and additional mutations, their impact on pathogenesis as well as their prognostic value, and how they may have future implications in therapeutic management.

Structured headache services as the solution to the ill-health burden of headache. 3. Modelling effectiveness and cost-effectiveness of implementation in Europe: findings and conclusions.

BACKGROUND: There have been several calls for estimations of costs and consequences of headache interventions to inform European public-health policies. In a previous paper, in the absence of universally accepted methodology, we developed headache-type-specific analytical models to be applied to implementation of structured headache services in Europe as the health-care solution to headache. Here we apply this methodology and present the findings. METHODS: Data sources were published evidence and expert opinions, including those from an earlier economic evaluation framework using the WHO-CHOICE model. We used three headache-type-specific analytical models, for migraine, tension-type-headache (TTH) and medication-overuse-headache (MOH). We considered three European Region case studies, from Luxembourg, Russia and Spain to include a range of health-care systems, comparing current (suboptimal) care versus target care (structured services implemented, with provider-training and consumer-education). We made annual and 5-year cost estimates from health-care provider and societal perspectives (2020 figures, euros). We expressed effectiveness as healthy life years (HLYs) gained, and cost-effectiveness as incremental cost-effectiveness-ratios (ICERs; cost to be invested/HLY gained). We applied WHO thresholds for cost-effectiveness. RESULTS: The models demonstrated increased effectiveness, and cost-effectiveness (migraine) or cost saving (TTH, MOH) from the provider perspective over one and 5 years and consistently across the health-care systems and settings. From the societal perspective, we found structured headache services would be economically successful, not only delivering increased effectiveness but also cost saving across headache types and over time. The predicted magnitude of cost saving correlated positively with country wage levels. Lost productivity had a major impact on these estimates, but sensitivity analyses showed the intervention remained cost-effective across all models when we assumed that remedying disability would recover only 20% of lost productivity. CONCLUSIONS: This is the first study to propose a health-care solution for headache, in the form of structured headache services, and evaluate it economically in multiple settings. Despite numerous challenges, we demonstrated that economic evaluation of headache services, in terms of outcomes and costs, is feasible as well as necessary. Furthermore, it is strongly supportive of the proposed intervention, while its framework is general enough to be easily adapted and implemented across Europe.

Structured headache services as the solution to the ill-health burden of headache. 2. Modelling effectiveness and cost-effectiveness of implementation in Europe: methodology.

BACKGROUND: Health economic evaluations support health-care decision-making by providing information on the costs and consequences of health interventions. No universally accepted methodology exists for modelling effectiveness and cost-effectiveness of interventions designed to close treatment gaps for headache disorders in countries of Europe (or elsewhere). Our aim here, within the European Brain Council's Value-of-Treatment project, was to develop headache-type-specific analytical models to be applied to implementation of structured headache services in Europe as the health-care solution to headache. METHODS: We developed three headache-type-specific decision-analytical models using the WHO-CHOICE framework and adapted these for three European Region country settings (Luxembourg, Russia and Spain), diverse in geographical location, population size, income level and health-care systems and for which we had population-based data. Each model compared current (suboptimal) care vs target care (delivered in accordance with the structured headache services model). Epidemiological and economic data were drawn from studies conducted by the Global Campaign against Headache; data on efficacy of treatments were taken from published randomized controlled trials; assumptions on uptake of treatments, and those made for Healthy Life Year (HLY) calculations and target-care benefits, were agreed with experts. We made annual and 5-year cost estimates from health-care provider (main analyses) and societal (secondary analyses) perspectives (2020 figures, euros). RESULTS: The analytical models were successfully developed and applied to each country setting. Headache-related costs (including use of health-care resources and lost productivity) and health outcomes (HLYs) were mapped across populations. The same calculations were repeated for each alternative (current vs target care). Analyses of the differences in costs and health outcomes between alternatives and the incremental cost-effectiveness ratios are presented elsewhere. CONCLUSIONS: This study presents the first headache-type-specific analytical models to evaluate effectiveness and cost-effectiveness of implementing structured headache services in countries in the European Region. The models are robust, and can assist policy makers in allocating health budgets between interventions to maximize the health of populations.

Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the "patient journey") with perplexing obstacles.High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary.The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded.It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.

Burden and attitude to resistant and refractory migraine: a survey from the European Headache Federation with the endorsement of the European Migraine & Headache Alliance.

BACKGROUND: New treatments are currently offering new opportunities and challenges in clinical management and research in the migraine field. There is the need of homogenous criteria to identify candidates for treatment escalation as well as of reliable criteria to identify refractoriness to treatment. To overcome those issues, the European Headache Federation (EHF) issued a Consensus document to propose criteria to approach difficult-to-treat migraine patients in a standardized way. The Consensus proposed well-defined criteria for resistant migraine (i.e., patients who do not respond to some treatment but who have residual therapeutic opportunities) and refractory migraine (i.e., patients who still have debilitating migraine despite maximal treatment efforts). The aim of this study was to better understand the perceived impact of resistant and refractory migraine and the attitude of physicians involved in migraine care toward those conditions. METHODS: We conducted a web-questionnaire-based cross-sectional international study involving physicians with interest in headache care. RESULTS: There were 277 questionnaires available for analysis. A relevant proportion of participants reported that patients with resistant and refractory migraine were frequently seen in their clinical practice (49.5% for resistant and 28.9% for refractory migraine); percentages were higher when considering only those working in specialized headache centers (75% and 46% respectively). However, many physicians reported low or moderate confidence in managing resistant (8.1% and 43.3%, respectively) and refractory (20.7% and 48.4%, respectively) migraine patients; confidence in treating resistant and refractory migraine patients was different according to the level of care and to the number of patients visited per week. Patients with resistant and refractory migraine were infrequently referred to more specialized centers (12% and 19%, respectively); also in this case, figures were different according to the level of care. CONCLUSIONS: This report highlights the clinical relevance of difficult-to-treat migraine and the presence of unmet needs in this field. There is the need of more evidence regarding the management of those patients and clear guidance referring to the organization of care and available opportunities.

Terapias complementarias en migraña y variables relacionadas. Encuesta Europea / Complementary therapies in migraine and related variables. European Survey

Objetivo: valorar el uso de terapias alternativas no farmacológicas en migraña y variables relacionadas. La migraña afecta a una de cada diez personas en el mundo, con aumento creciente y mayor prevalencia entre mujeres de zonas urbanas. Aunque los tratamientos habituales son farmacológicos, se ha incrementado el uso de terapias alternativas no farmacológicas en migraña y variables relacionadas. Materiales y métodos: estudio observacional transversal mediante encuesta anónima vía web a 3.342 pacientes de países europeos sobre el uso de terapias alternativas para tratamiento de migraña. Variables de estudio: edad, género, país, tipo de localidad, nivel de estudios, ámbito rural o urbano y respuesta al tratamiento. Resultados: la utilización de terapias alternativas en migraña es un fenómeno creciente, con mayor uso en pacientes entre 41-60 años y estudios superiores. Conclusiones: en migraña se observan diferencias por edad, género, nivel cultural y país de procedencia. El uso de la medicina complementaria como alternativa terapéutica en la migraña es poco habitual y se debería indagar con mayor profundidad estableciendo relaciones que permitan apoyar al paciente afectado y priorizar las de mayor evidencia científica..(Au)

Objective: to evaluate the use of alternative non-pharmacological therapies in migraine and related variables. Migraine affects one in ten people worldwide, with a growing increase and a higher prevalence among women in urban areas. Although the usual treatments are pharmacological, the use of alternative techniques is increasing. Materials and methods: cross-sectional observational study by anonymous web survey of 3,342 patients from European countries on the use of alternative therapies. Study variables: age, gender, country, type of locality, educational level, rural or urban setting and treatment response. Results: the use of alternative therapies in migraine treatment is a growing phenomenon, with greater use in patients between 41-60 years of age and higher education. Conclusions: in Migraine, differences are observed by age, gender, cultural level and country of origin. The use of complementary medicine as an therapeutic alternative in migraine is uncommon and should be investigated in greater depth, establishing relationships that allow supporting the affected patient and prioritizing, if possible, some over others with scientific evidence..(Au)