InterMiG: international differences in the therapeutic approach to migraine patients in specialized headache centers

Antidepressiu; Migranya; Tractament preventiuAntidepresivo; Migraña; Tratamiento preventivoAntidepressant; Migraine; Preventive treatmentBackground There is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences. Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries. Methods This is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months. Results A total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %). Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p < 0.0001); antiepileptic drugs were more frequently prescribed in Portugal, Australia and Spain (AU: 73.3 %, IT: 40.0 %, DE: 37.5 %, PL: 48.9 %, PT: 85.0 %, RUS: 29.4 % and ES: 69.0 %; p < 0.0001); beta-blockers and antihypertensive drugs were frequently used in all countries except Italy (AU: 60.0 %, IT: 14.0 %, DE: 53.8 %, PL: 48.9 %, PT: 68.3 %, RUS: 49.4 % and ES: 59.0 %; p < 0.0001); BTX-A were predominately used in Spain, Italy and Australia (AU:56.7 %, IT:58.0 %, DE:20.0 %, PL: 42.2 %, PT: 26.7 %, RUS: 24.7 % and ES: 58.5 %; p < 0.0001) and others were most frequently used in Poland (AU: 0.0 %, IT: 19.0 %, DE: 42.5 %, PL: 95.6 %, PT: 31.7 %, RUS: 3.5 % and ES: 49.5 %; p < 0.0001). If only patients without comorbidities are considered (200/600), statistically differences between countries persist in all preventive treatments. Conclusions There is heterogeneity in the choice of preventive treatment between different countries. Prospective comparative studies of the different oral and subcutaneous alternatives would help to create a global therapeutic algorithm that would guarantee the best option for our patients.This work did not receive any funds

Exploring sensory sensitivity, cortical excitability, and habituation in episodic migraine, as a function of age and disease severity, using the pattern-reversal task

Cortical excitability; Migraine; Visual sensitivityExcitabilitat cortical; Migranya; Sensibilitat visualExcitabilidad cortical; Migraña; Sensibilidad visualBackground Migraine is a cyclic, neurosensory disorder characterized by recurrent headaches and altered sensory processing. The latter is manifested in hypersensitivity to visual stimuli, measured with questionnaires and sensory thresholds, as well as in abnormal cortical excitability and a lack of habituation, assessed with visual evoked potentials elicited by pattern-reversal stimulation. Here, the goal was to determine whether factors such as age and/or disease severity may exert a modulatory influence on sensory sensitivity, cortical excitability, and habituation. Methods Two similar experiments were carried out, the first comparing 24 young, episodic migraine patients and 28 healthy age- and gender-matched controls and the second 36 middle-aged, episodic migraine patients and 30 healthy age- and gender-matched controls. A neurologist confirmed the diagnoses. Migraine phases were obtained using eDiaries. Sensory sensitivity was assessed with the Sensory Perception Quotient and group comparisons were carried out. We obtained pattern-reversal visual evoked potentials and calculated the N1-P1 Peak-to-Peak amplitude. Two linear mixed-effects models were fitted to these data. The first model had Block (first block, last block) and Group (patients, controls) as fixed factors, whereas the second model had Trial (all trials) and Group as fixed factors. Participant was included as a random factor in both. N1-P1 first block amplitude was used to assess cortical excitability and habituation was defined as a decrease of N1-P1 amplitude across Blocks/Trials. Both experiments were performed interictally. Results The final samples consisted of 18 patients with episodic migraine and 27 headache-free controls (first experiment) and 19 patients and 29 controls (second experiment). In both experiments, patients reported increased visual hypersensitivity on the Sensory Perception Quotient as compared to controls. Regarding N1-P1 peak-to-peak data, there was no main effect of Group, indicating no differences in cortical excitability between groups. Finally, significant main effects of both Block and Trial were found indicating habituation in both groups, regardless of age and headache frequency. Conclusions The results of this study yielded evidence for significant hypersensitivity in patients but no significant differences in either habituation or cortical excitability, as compared to headache-free controls. Although the alterations in patients may be less pronounced than originally anticipated they demonstrate the need for the definition and standardization of optimal methodological parameters.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: AMM salary has been partially financed by a predoctoral grant from the “Fundacio Institut de Recerca Hospital Universitari Vall d’Hebron” (VHIR/BEQUESPREDOC/2020/MARTI). AVB salary has been partially financed by a Juan de la Cierva-Formacion grant (FJC2018-036804-I) and a Juan de la Cierva-Incorporación grant (IJC2020-043139-I) from the Spanish Ministry of Science and Innovation. XCC salary has been co-funded by the European Regional Development Fund (001-P-001682) under the framework of the FEDER Operative Programme for Catalunya 2014–2020, with 1,527,637.88 euros. EC salary has been funded by Rıo Hortega grant Accion Estrategica en Salud 2017–2020, Instituto de Salud Carlos III (CM20/00217). SSF has been supported by grants from the Ministerio de Ciencia e Innovación (PID2019-108531 GB-I00 AEI/FEDER) and AGAUR Generalitat de Catalunya (2021 SGR 00911). The project leading to these results has received funding from “la Caixa” Foundation under the project code “LCF/PR/PR16/51110005”

Decarbonising the transport and energy sectors: Technical feasibility and socioeconomic impacts in Costa Rica

Compliance with the Paris Agreement requires the transformation of national economies to meet net-zero carbon dioxide emissions by mid-century. To accomplish this, countries need to define long-term decarbonisation strategies with near- and mid-term actions to determine their ideal future scenario while maximizing socioeconomic benefits. This paper describes the process followed to support the creation of the decarbonisation pathway for the transport and energy sectors presented in Costa Rica's National Decarbonisation Plan. We discuss in detail the technological pathway of a deep-decarbonisation future that supports reaching net-zero emissions by 2050. Compared to a business-as-usual (BAU) scenario, our results show that the decarbonisation pathway can lead to emissions' reduction of 87% in the transport and energy sectors by 2050. Energy efficiency, the adoption of electromobility, modal-shift towards public transport and active mobility, as well as reduced demand due to digitalisation and teleworking, are found to be key drivers towards the deep-decarbonisation. These measures combined enable a 25% reduction of primary energy production by 2050. The results highlight that the decarbonisation scenario requires installing 4.4 GW more of renewable power plants by 2050, compared to the BAU scenario (80%). We also show that additional investments for the deep-decarbonisation are compensated with the reduced operating cost. Crucially, we found that the National Decarbonisation Plan results in a lower total discounted cost of about 35% of current Costa Rica's GDP, indicating that a deep decarbonisation is technically feasible and is coupled to socioeconomic benefits

Hospital-based proton therapy implementation during the COVID pandemic: early clinical and research experience in a European academic institution

Introduction A rapid deploy of unexpected early impact of the COVID pandemic in Spain was described in 2020. Oncology practice was revised to facilitate decision-making regarding multimodal therapy for prevalent cancer types amenable to multidisciplinary treatment in which the radiotherapy component searched more efcient options in the setting of the COVID-19 pandemic, minimizing the risks to patients whilst aiming to guarantee cancer outcomes. Methods A novel Proton Beam Therapy (PBT), Unit activity was analyzed in the period of March 2020 to March 2021. Institutional urgent, strict and mandatory clinical care standards for early diagnosis and treatment of COVID-19 infection were stablished in the hospital following national health-authorities’ recommendations. The temporary trends of patients care and research projects proposals were registered. Results 3 out of 14 members of the professional staf involved in the PBR intra-hospital process had a positive test for COVID infection. Also, 4 out of 100 patients had positive tests before initiating PBT, and 7 out of 100 developed positive tests along the weekly mandatory special checkup performed during PBT to all patients. An update of clinical performance at the PBT Unit at CUN Madrid in the initial 500 patients treated with PBT in the period from March 2020 to November 2022 registers a distribution of 131 (26%) pediatric patients, 63 (12%) head and neck cancer and central nervous system neoplasms and 123 (24%) re-irradiation indications. In November 2022, the activity reached a plateau in terms of patients under treatment and the impact of COVID pandemic became sporadic and controlled by minor medical actions. At present, the clinical data are consistent with an academic practice prospectively (NCT05151952). Research projects and scientifc production was adapted to the pandemic evolution and its infuence upon professional time availability. Seven research projects based in public funding were activated in this period and preliminary data on molecular imaging guided proton therapy in brain tumors and post-irradiation patterns of blood biomarkers are reported. Conclusions Hospital-based PBT in European academic institutions was impacted by COVID-19 pandemic, although clinical and research activities were developed and sustained. In the post-pandemic era, the benefts of online learning will shape the future of proton therapy education

The Sorcerer II Global Ocean Sampling Expedition: Northwest Atlantic through Eastern Tropical Pacific

The world's oceans contain a complex mixture of micro-organisms that are for the most part, uncharacterized both genetically and biochemically. We report here a metagenomic study of the marine planktonic microbiota in which surface (mostly marine) water samples were analyzed as part of the Sorcerer II Global Ocean Sampling expedition. These samples, collected across a several-thousand km transect from the North Atlantic through the Panama Canal and ending in the South Pacific yielded an extensive dataset consisting of 7.7 million sequencing reads (6.3 billion bp). Though a few major microbial clades dominate the planktonic marine niche, the dataset contains great diversity with 85% of the assembled sequence and 57% of the unassembled data being unique at a 98% sequence identity cutoff. Using the metadata associated with each sample and sequencing library, we developed new comparative genomic and assembly methods. One comparative genomic method, termed “fragment recruitment,” addressed questions of genome structure, evolution, and taxonomic or phylogenetic diversity, as well as the biochemical diversity of genes and gene families. A second method, termed “extreme assembly,” made possible the assembly and reconstruction of large segments of abundant but clearly nonclonal organisms. Within all abundant populations analyzed, we found extensive intra-ribotype diversity in several forms: (1) extensive sequence variation within orthologous regions throughout a given genome; despite coverage of individual ribotypes approaching 500-fold, most individual sequencing reads are unique; (2) numerous changes in gene content some with direct adaptive implications; and (3) hypervariable genomic islands that are too variable to assemble. The intra-ribotype diversity is organized into genetically isolated populations that have overlapping but independent distributions, implying distinct environmental preference. We present novel methods for measuring the genomic similarity between metagenomic samples and show how they may be grouped into several community types. Specific functional adaptations can be identified both within individual ribotypes and across the entire community, including proteorhodopsin spectral tuning and the presence or absence of the phosphate-binding gene PstS

Cruise Summary Report - MEDWAVES survey. MEDiterranean out flow WAter and Vulnerable EcosystemS (MEDWAVES)

The MEDWAVES (MEDiterranean out flow WAter and Vulnerable EcosystemS) cruise targeted areas under the potential influence of the MOW within the Mediterranean and Atlantic realms. These include seamounts where Cold-water corals (CWCs) have been reported but that are still poorly known, and which may act as essential “stepping stones” connecting fauna of seamounts in the Mediterranean with those of the continental shelf of Portugal, the Azores and the Mid-Atlantic Ridge. During MEDWAVES sampling has been conducted in two of the case studies of ATLAS: Case study 7 (Gulf of Cádiz-Strait of Gibraltar-Alboran Sea) and Case study 8 (Azores). The initially targeted areas in the Atlantic were: the Gazul Mud volcano, in the Gulf of Cádiz (GoC) area, included in the case study 7, and the Atlantic seamounts Ormonde (Portuguese shelf) and Formigas (by Azores), both part of the case study 8. In the Mediterranean the targeted areas were The Guadiaro submarine canyon and the Seco de los Olivos (also known as Chella Bank) seamount. Unfortunately it was not possible to sample in Guadiaro due to time constraints originated by adverse meteorological conditions which obligate us to reduce the time at sea focusing only in 4 of the 5 initially planned areas. MEDWAVES was structured in two legs; the first leg took place from the 21st September (departure from Cádiz harbour in Spain) to the 13th October 2016 (arrival in Ponta Delgada, São Miguel, Azores, Portugal took place the 8th of October due to the meteorological conditions that obligated to conclude the first leg earlier as planned). during the Leg 1 sampling was carried out in Gazul, Ormonde and Formigas. The second leg started the 14th October (departure from Ponta Delgada) and finished the 26th October (arrival in Málaga harbour, Spain). MEDWAVES had a total of 30 effective sampling days, being 6 days not operative due to the adverse meteorological conditions experienced during the first leg which forced us to stay in Ponta Delgada from the 08th to the 13th October. During MEDWAVES the daily routine followed a similar scheme, depending of course on the weather and sea conditions. The main activity during the day, starting early in the morning (around 08:00 AM, once the night activities were finished), was the ROV deployment. Generally a single ROV dive of around 8 hours was performed, however in several occasions two dives were carried out in the same day (see General station list, Appendix II). After the ROV (and sometimes between two dives) the Box Corer and/or Van Veen Grab and/or Multicore was deployed. After these activities, during the night CTD-Rosette deployments and MB was conducted. Accordingly to this schema the scientific personnel worked in the day or in the night watch. A total of 215 sampling stations have been covered in MEDWAVES, using the following sampling gears: Multibeam echosounder, CTD-Rosette, LADCP, Box Corer, Van Veen Grab, Multicorer and a Remotely Operated Vehicle (ROV). Table 1 sumamrised the number of sampling stations conducted with each gear in each sampling zone. Additionally MB surveys have been conducted during the transits between area

Health enhancing strength training in nonagenarians (STRONG): rationale, design and methods

<p>Abstract</p> <p>Background</p> <p>The Health Enhancing Strength Training in Nonagenarians (STRONG) is a randomised control trial to assess the effectiveness of an aerobic and strength training program for improving muscle strength, functional capacity and quality of life in nonagenarians.</p> <p>Methods</p> <p>Sixty (51 women) nonagenarians (age range: 90–102 years) who live in a geriatric nursing home will be randomly assigned to either a usual care (control) group (n = 30) or an intervention (training) group (n = 30). Participants allocated in the usual care group will receive general physical activity guidelines and participants allocated in the intervention group will also enrol in three weekly non-consecutive individualized training sessions (~45–50 min each) during 8 weeks. The exercise program will consist of muscular strength [with a special focus on leg press at 30% (start of the program) to 70% 1 repetition maximum (end)] and aerobic exercises (cycle-ergometry during 3–5 to 15 minutes at 12–14 points in the rate of perceived exertion scale).</p> <p>Results</p> <p>Results from STRONG will help to better understand the potential of regular physical activity for improving the well-being of the oldest population groups.</p> <p>Conclusion</p> <p>The increase in life expectancy together with the dramatic decrease in birth rates in industrialized countries calls the attention to health care systems and public health policymakers to focus attention on promoting healthy lifestyle in the highest sector of the population pyramid. Our study attempts to improve functional capacity and QOL of nonagenarians by implementing an individualised aerobic and strength training program in a geriatric residential care. Results from STRONG will help to better understand the potential of regular physical activity for improving the well being even in persons aged 90 years or over.</p> <p>Trail Registration</p> <p>ClinicalTrials.gov ID: NCT00848978</p

Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor

Objective: The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights. Methods: A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses. Results: The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. Interpretation: This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor