European Headache Federation (EHF) consensus on the definition of effective treatment of a migraine attack and of triptan failure

Attack; Migraine; TriptanAtaque; Migraña; TriptánAtac; Migranya; TriptanBackground Triptans are migraine-specific acute treatments. A well-accepted definition of triptan failure is needed in clinical practice and for research. The primary aim of the present Consensus was to provide a definition of triptan failure. To develop this definition, we deemed necessary to develop as first a consensus definition of effective treatment of an acute migraine attack and of triptan-responder. Main body The Consensus process included a preliminary literature review, a Delphi round and a subsequent open discussion. According to the Consensus Panel, effective treatment of a migraine attack is to be defined on patient well-being featured by a) improvement of headache, b) relief of non-pain symptoms and c) absence of adverse events. An attack is considered effectively treated if patient’s well-being, as defined above, is restored within 2 hours and for at least 24 hours. An individual with migraine is considered as triptan-responder when the given triptan leads to effective acute attack treatment in at least three out of four migraine attacks. On the other hand, an individual with migraine is considered triptan non-responder in the presence of failure of a single triptan (not matching the definition of triptan-responder). The Consensus Panel defined an individual with migraine as triptan-resistant in the presence of failure of at least 2 triptans; triptan refractory, in the presence of failure to at least 3 triptans, including subcutaneous formulation; triptan ineligibile in the presence of an acknowledged contraindication to triptan use, as specified in the summary of product characteristics. Conclusions The novel definitions can be useful in clinical practice for the assessment of acute attack treatments patients with migraine. They may be helpful in identifying people not responding to triptans and in need for novel acute migraine treatments. The definitions will also be of help in standardizing research on migraine acute care.This work is supported by a grant from the European Headache Federation to cover publication fees

Therapeutic Management: When and What

Migraine is a widespread brain disease that is classified as the second most disabling condition and has the third highest prevalence of all medical conditions. Despite its non-emergent or life-threatening nature, migraine can progress to chronic type, a subform associated with significant morbidity and drug overuse. In the management of migraine, it is important therefore to introduce early prophylactic treatment in order to limit migraine chronification. In this chapter, we will go through all the treatment options, both acute and preventive, pharmaceutical and non-pharmaceutical following this flowchart: 1. Introduction; 2. General principles; 2.1 Symptomatic therapy; 2.2 Prophylactic management; 3. Pharmaceutical therapies; 3.1 Symptomatic; 3.1.1 Disease-specific; 3.1.2 No disease-specific; 3.2 Prophylactic; 3.2.1 Disease-specific; 3.2.2 No disease-specific; 3.3 Non-Pharmaceutical therapies; 3.4 Neuromodulation; 3.4.1 Invasive; 3.4.5 Non-invasive; 3.5 Nutrient (nutraceuticals); 3.6 Dietary interventions; 3.7 Acupuncture; 3.8 Physical therapy; 4. Cognitive behavioral therapies; 5. Patient centricity and patient education

The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis

OBJECTIVE: While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist random-effects network meta-analysis and rated the certainty (quality) of evidence as either high, moderate, low, or very low using the GRADE approach. RESULTS: We identified 74 eligible trials, reporting on 32,990 patients. We found high certainty evidence that monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP(r)mAbs), gepants, and topiramate increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo. We found moderate certainty evidence that beta-blockers, valproate, and amitriptyline increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, and low certainty evidence that gabapentin may not be different from placebo. We found high certainty evidence that, compared to placebo, valproate and amitriptyline lead to substantial adverse events leading to discontinuation, moderate certainty evidence that topiramate, beta-blockers, and gabapentin increase adverse events leading to discontinuation, and moderate to high certainty evidence that (CGRP(r)mAbs) and gepants do not increase adverse events. CONCLUSIONS: (CGRP(r)mAbs) have the best safety and efficacy profile of all drugs for migraine prophylaxis, followed closely by gepants.info:eu-repo/semantics/publishedVersio

Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis

Objective: To compare all licensed drug interventions as oral monotherapy for the acute treatment of migraine episodes in adults. Design: Systematic review and network meta-analysis. Data sources: Cochrane Central Register of Controlled Trials, Medline, Embase, ClinicalTrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, as well as websites of regulatory agencies and pharmaceutical companies without language restrictions until 24 June 2023. Methods: Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Random effects network meta-analyses were conducted for the primary analyses. The primary outcomes were the proportion of participants who were pain-free at two hours post-dose and the proportion of participants with sustained pain freedom from two to 24 hours post-dose, both without the use of rescue drugs. Certainty of the evidence was graded using the confidence in network meta-analysis (CINeMA) online tool. Vitruvian plots were used to summarise findings. An international panel of clinicians and people with lived experience of migraine co-designed the study and interpreted the findings. Eligibility criteria for selecting studies: Double blind randomised trials of adults (≥18 years) with a diagnosis of migraine according to the International Classification of Headache Disorders. Results: 137 randomised controlled trials comprising 89 445 participants allocated to one of 17 active interventions or placebo were included. All active interventions showed superior efficacy compared with placebo for pain freedom at two hours (odds ratios from 1.73 (95% confidence interval (CI) 1.27 to 2.34) for naratriptan to 5.19 (4.25 to 6.33) for eletriptan), and most of them also for sustained pain freedom to 24 hours (odds ratios from 1.71 (1.07 to 2.74) for celecoxib to 7.58 (2.58 to 22.27) for ibuprofen). In head-to-head comparisons between active interventions, eletriptan was the most effective drug for pain freedom at two hours (odds ratios from 1.46 (1.18 to 1.81) to 3.01 (2.13 to 4.25)), followed by rizatriptan (1.59 (1.18 to 2.17) to 2.44 (1.75 to 3.45)), sumatriptan (1.35 (1.03 to 1.75) to 2.04 (1.49 to 2.86)), and zolmitriptan (1.47 (1.04 to 2.08) to 1.96 (1.39 to 2.86)). For sustained pain freedom, the most efficacious interventions were eletriptan and ibuprofen (odds ratios from 1.41 (1.02 to 1.93) to 4.82 (1.31 to 17.67)). Confidence in accordance with CINeMA ranged from high to very low. Sensitivity analyses on Food and Drug Administration licensed doses only, high versus low doses, risk of bias, and moderate to severe headache at baseline confirmed the main findings for both primary and secondary outcomes. Conclusions: Overall, eletriptan, rizatriptan, sumatriptan, and zolmitriptan had the best profiles and they were more efficacious than the recently marketed drugs lasmiditan, rimegepant, and ubrogepant. Although cost effectiveness analyses are warranted and careful consideration should be given to patients with a high risk cardiovascular profile, the most effective triptans should be considered as preferred acute treatment for migraine and included in the WHO List of Essential Medicines to promote global accessibility and uniform standards of care. Systematic review registration: Open Science Framework https://osf.io/kq3ys/

Placebo responses vary by route of administration in migraine prevention trials. What does this mean?

Placebo responses vary by route of administration in migraine prevention trials. What does this mean

Adsorption of copper on olive pomace activated biochar

Περίληψη: Ο σκοπός της διπλωματικής εργασίας είναι η προσρόφηση χαλκού Cu (II) από υδατικό διάλυμα σε βιοεξανθράκωμα (biochar) ελαιοπυρήνα. Πραγματοποιήθηκαν πειράματα με χρήση ολόκληρου του ελαιοπυρήνα, αλλά και ξεχωριστά μόνο με το κουκούτσι και την πούλπα, όλα εκ των οποίων πυρολύθηκαν στους 400 oC. Επίσης, μελετήθηκε η προσρόφηση χαλκού σε βιοεξανθρακώματα (ολόκληρο, κουκούτσι, πούλπα) μετά από επεξεργασία με υδροξείδιο του καλίου (KOH) και χλωριούχο ψευδάργυρο (ZnCl2) στους 800 oC. Tο σύνολο των πυρολυμένων δειγμάτων χαρακτηρίστηκε ως προς το pH, την περιεχόμενη τέφρα, την στοιχειακή τους ανάλυση, τον προσδιορισμό μετάλλων, την ειδική επιφάνεια (ΒΕΤ) και τη φασματοσκοπία (FTIR). Τα ανεπεξέργαστα υλικά χαρακτηρίστηκαν επίσης και ως προς την υγρασία τους, τα πτητικά στερεά και τον μόνιμο άνθρακα. Στη συνέχεια, πραγματοποιήθηκαν μια σειρά από πειράματα προσρόφησης, τα οποία έδειξαν ότι τα υλικά που υπέστησαν χημική επεξεργασία από KOH και ZnCl2 δεν ήταν αποτελεσματικά για την προσρόφηση Cu (II). Ακολούθως, εκτελέστηκαν πειράματα κινητικής προσρόφησης του χαλκού Cu (II) μόνο στα μη χημικά επεξεργασμένα βιοεξανθρακώματα. Τα αποτελέσματα έδειξαν πως η πούλπα του ελαιοπυρήνα λειτουργεί εμφανώς καλύτερα για απομάκρυνση χαλκού και έτσι, ακολούθησαν τα πειράματα της ισορροπίας προσρόφησης του χαλκού Cu (II) μόνο για την πούλπα. Συνολικά, μελετήθηκε η επίδραση τεσσάρων παραγόντων και συγκεκριμένα του pH, του χρόνου επαφής, της θερμοκρασίας και της συγκέντρωσης Cu (II) στο διάλυμα. Τα βιοεξανθρακώματα υλικά έδειξαν τόσο θετική όσο και αρνητική επιρροή σε όλους τους εξεταζόμενους παράγοντες, καθώς και ελαφρώς διαφορετική συμπεριφορά, λόγω της διαφορετικής τους σύστασης. Επίσης, εφαρμόστηκαν 6 μοντέλα για την επεξεργασία των αποτελεσμάτων των πειραμάτων της κινητικής και της ισορροπίας προσρόφησης. Πιο συγκεκριμένα, εφαρμόστηκαν τα μοντέλα ψευδο-πρώτης τάξης, ψευδο-δεύτερης τάξης και διασωματιδιακής διάχυσης για την κινητική και τα μοντέλα γραμμικής ισόθερμης, ισόθερμης Freundlich και ισόθερμης Langmuir για την ισορροπία προσρόφησης. Τα μοντέλα που περιγράφουν πιο ικανοποιητικά τα υπό μελέτη προσροφούμενα υλικά είναι το μοντέλο ψευδο-δεύτερης τάξης για την κινητική προσρόφησης και τα μοντέλα Ισόθερμης Freundlich και Langmuir συνδυαστικά για την ισορροπία προσρόφησης. Συμπερασματικά, παρατηρείται ότι, το υλικό που παρουσίασε το καλύτερο αποτελέσματα ήταν η πούλπα πυρολυμένη στους 400 βαθμούς Κελσίου χωρίς περεταίρω χημική επεξεργασία, και συγκεκριμένα επεξεργασμένη με pH 6, με χρόνο επαφής 4 ώρες, θερμοκρασία 45 °C και για 10 mg/L χαλκού CU (ΙΙ) συγκέντρωση στο διάλυμα.Summarization: The main objective of the dissertation is the adsorption of copper Cu (II) from an aqueous solution to biochar from olive pit. Experiments were conducted using not only the entire olive pit, but also using separately its kernel and pulp, all of which were pyrolyzed at 400 oC. In addition, the adsorption of copper on biochar (whole, kernel, pulp) after treatment with potassium hydroxide (KOH) and zinc chloride (ZnCl2) at 800 oC was studied. All pyrolyzed samples were characterized in terms of pH, ash content, elemental composition, metal determination, specific surface area (BET) and spectroscopy (FTIR). The unprocessed materials were also characterized in reference to their moisture content, volatile mater content and permanent carbon content. A series of adsorption experiments were then performed, which showed that the materials treated with KOH and ZnCl2 were not effective in adsorbing Cu (II). Subsequently, kinetic adsorption experiments of copper Cu (II) were performed only on non-chemically treated biochars. The results showed that the olive pulp biochar worked significantly better for copper adsorption and thus, the Cu (II) copper adsorption equilibrium experiments were only conducted for the pulp biochar. In total, the effect of four factors was studied, namely pH, contact time, temperature and Cu (II) concentration in the solution. The biochars showed both positive and negative influence on all the examined factors, as well as slightly different behavior, due to their different composition. In addition, 6 models were applied to process the results of the kinetic and the adsorption equilibrium experiments. More specifically, pseudo-first order, pseudo-second order and intraparticle diffusion models were applied for the kinetic experiments and linear isotherm, Freundlich isotherm and Langmuir isotherm models were applied for the absorption equilibrium experiments. The models that most satisfactorily describe the materials studied are the pseudo-second order model for the kinetic experiments and the Freundlich and Langmuir isotherm models in combination for the adsorption equilibrium. In conclusion, the material that showed the best results was the pulp, which was pyrolyzed at 400 oC without further chemical treatment and specifically treated at pH 6, with a contact time of 4 hours, temperature 45 ° C and for 10 mg / L copper CU (II) concentration in the solution

Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence—What Do We Know So Far?

Now more than ever is the time of monoclonal antibody use in neurology. In headaches, disease-specific and mechanism-based treatments existed only for symptomatic management of migraines (i.e., triptans), while the standard prophylactic anti-migraine treatments consist of non-specific and repurposed drugs that share limited safety profiles and high risk for interactions with other medications, resulting in rundown adherence rates. Recent advances in headache science have increased our understanding of the role of calcitonin gene relate peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) pathways in cephalic pain neurotransmission and peripheral or central sensitization, leading to the development of monoclonal antibodies (mAbs) or small molecules targeting these neuropeptides or their receptors. Large scale randomized clinical trials confirmed that inhibition of the CGRP system attenuates migraine, while the PACAP mediated nociception is still under scientific and clinical investigation. In this review, we provide the latest clinical evidence for the use of anti-CGRP in migraine prevention with emphasis on efficacy and safety outcomes from Phase III and real-world studies