1,721,012 research outputs found
Erenumab per il trattamento preventivo dell'emicrania cronica: efficacia e sicurezza fino a un anno, predittori di risposta ed effetti della sospensione.
No full textL'emicrania cronica (CM) colpisce circa l'1-2% della popolazione generale e rappresenta un onere significativo per la società. Inoltre, la sua gestione clinica è complessa e complicata dalla carenza di trattamenti preventivi e dalla frequente associazione con il mal di testa da uso eccessivo di farmaci (MOH). Infatti, i malati di CM spesso assumono elevate quantità di antidolorifici che possono paradossalmente peggiorare il CM, imponendo così una sospensione dell'antidolorifico prima che possa essere iniziato un nuovo trattamento preventivo. La scoperta del coinvolgimento del peptide correlato al gene della calcitonina (CGRP) nella patogenesi della CM ha cambiato completamente il trattamento della CM. Erenumab è un anticorpo monoclonale contro il recettore CGRP disponibile in Italia per il trattamento del CM dal 2019. In tale studio si è esplorata l'efficacia e la sicurezza a lungo termine di questo farmaco fino a 1 anno di trattamento e i predittori clinici della risposta ad esso. Inoltre, è stata esplorata l'evoluzione clinica dei pazienti che interrompono erenumab a causa del completamento del trattamento, come i predittori clinici di un eventuale peggioramento di CM e MOH. I nostri risultati hanno dimostrato che erenumab è efficace e sicuro fino a un anno di trattamento. Inoltre, i diversi dosaggi di erenumab hanno mostrato un'efficacia simile e la risposta dei pazienti è stata simile tra quelli che stavano ancora assumendo un farmaco preventivo al basale e quelli che non lo assumevano. Dopo un anno di trattamento, i potenziali predittori clinici di una peggiore risposta a erenumab erano: la presenza di una storia più lunga di cefalea da uso eccessivo di farmaci (MOH) al basale, un numero maggiore di antidolorifici assunti al mese al basale e un numero di trattamenti preventivi falliti al basale. Erenumab ha dimostrato di essere ugualmente efficace negli uomini e nelle donne. Inoltre, l'efficacia di erenumab non è stata influenzata dalla precedente detossificazione da farmaci analgesici. La sospensione di erenumab dopo 1 anno di trattamento è stata associata a un generale peggioramento della recidiva di CM e MOH. Inoltre, un maggiore BMI, l'assenza di aura e la presenza di un numero maggiore di giorni di emicrania, nonché un maggiore consumo di antidolorifici al basale, erano significativamente associati a questo peggioramento. I nostri risultati mostrano che i malati di CM trattati con erenumab hanno mostrato un miglioramento significativo che si mantiene fino a un anno. Ad ogni modo, dopo aver interrotto il farmaco, il CM di solito peggiora e il MOH si ripresenta. È molto probabile che i pazienti con una compromissione più elevata al basale ottengano minori benefici con erenumab e sperimentino una ricaduta di CM e MOH dopo la sospensione del trattamento. Questi risultati hanno dimostrato che, nonostante la buona efficacia, erenumab non è un agente modificante la malattia nel CM e che altri attori oltre al CGRP possono influenzare la patogenesi del CM. Inoltre, tutti i fattori che possono aumentare i livelli di CGRP, come un numero elevato di giorni di emicrania al mese o una lunga durata di MOH, possono ridurre l'efficacia di erenumab. Infine, anche fattori che possono potenziare indirettamente l'azione del CGRP, come l'indice di massa corporea, possono ridurre l'efficacia di erenumab.Chronic migraine (CM) affects about the 1-2% of the general population and imposes a significant burden on the society. Moreover, its clinical management is complex and complicated by the shortage of preventive treatments and the frequent association with medication overuse-headache (MOH). Indeed, CM sufferers often take high quantities of painkillers that may paradoxically worsen CM, thus imposing a painkiller withdrawal before a new preventive treatment could be started. The discovery of the involvement of the calcitonin gene-related peptide (CGRP) in the pathogenesis of CM has completely changed the treatment of CM. Erenumab is a monoclonal antibody against the CGRP receptor that is available in Italy for the treatment of CM since 2019. Here, we have explored the long-term effectiveness and safety of this drug up to 1 year of treatment and the clinical predictors of the response to it. Moreover, the clinical evolution of the patients stopping erenumab due to the treatment completion will be explored, such as the clinical predictors of an eventual worsening of CM and MOH. Our results demonstrated that erenumab was effective and safe up to one year of treatment. Moreover, the different dosages of erenumab showed a similar effectiveness and patients’ response was similar between the ones who were still taking a preventive medication at the baseline and the ones who weren’t. After one year of treatment, potential clinical predictors of a worst response to erenumab were: the presence of a longer history of medication overuse-headache (MOH) at the baseline, a higher number of painkillers taken per month at the baseline, and a higher number of failed preventive treatments at the baseline. Erenumab has been proven to be equally effective in men and women. Moreover, the effectiveness of erenumab was not influenced by the withdrawal of painkillers before stating it. The suspension of erenumab after 1 year of treatment was associated with a general worsening of CM and MOH relapse. Furthermore, a higher BMI, the absence of aura and the presence of a higher number of migraine days as well as a higher painkiller consumption at the baseline were significantly associated with this worsening. Our results show that CM sufferers treated with erenumab displayed a significant amelioration which is maintained up to one year. Anyway, after stopping the drug, CM usually worses and the MOH relapses. Patients with a higher impairment at the baseline are much likely to gain less benefits with erenumab and to experience a CM and MOH relapse after treatment suspension. These results demonstrated that, despite the good effectiveness, erenumab is not a disease-modifying agent in CM and that other actors besides CGRP may influence CM pathogenesis. Furthermore, all the factors that may increase CGRP levels, such as a high number of migraine days per month or a long duration of MOH may reduce the effectiveness of erenumab. Finally, even factors that may indirectly potentiate the CGRP action, such as the body mass index, may reduce the effectiveness of erenumab
Medication overuse and chronic migraine: a critical review according to clinical pharmacology
No full textChronic migraine is often complicated by medication-overuse headache (MOH), a headache due to excessive intake of acute medications. Chronic migraine and MOH are serious and disabling disorders. Since chronic migraine derives from the progression of originally episodic migraine, the fundamental therapeutic strategy is prevention. This narrative review describes how to try to prevent the development of MOH and how to manage it once it has appeared. Areas covered: A PubMed database search (from 1988 to January 2015) and a review of published studies on chronic migraine and MOH were conducted. Expert opinion: In spite of progress in migraine treatment, the prevalence of chronic headaches and MOH has not changed in the course of time. Today, a large number of migraine patients have turned to numerous expert physicians and experienced all sorts of prophylactic treatments without decisive benefits. Their condition seems to have crystallized even more as chronic and intractable. This means that to prevent chronification and MOH, we need more effective drugs and better strategies to use them. In particular, we must detect disease biomarkers and predictive factors for drug response that allow for personalized treatment when migraine is still episodic and make analgesic overuse pointless
Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) with monoclonal antibodies in migraine prevention: a brief review
Get PDFIntroduction
Interest is growing in the role of pituitary adenylate cyclase-activating polypeptide (PACAP) and its specific PAC1 receptor in migraine and in their antagonism as a strategy for migraine prevention.
Areas covered
We discuss and critically evaluate (i) the evidence of the role of PACAP in migraine pathophysiology and (ii) the first clinical trials in migraine prophylaxis with monoclonal antibodies AMG 301 and ALD1910 which act against PAC1 and PACAP38 respectively. We examined PubMed, Scopus, and ClinicalTrials.gov electronic databases to examine the relevant material.
Expert opinion
There is much proof of the ability of PACAP to cause migraine, but there is limited evidence that blocking PACAP or PAC1 receptor can prevent migraine. However, the potential of anti-PACAP antibodies in migraine prophylaxis is high. Theoretically, if these antibodies block the activation of the trigeminovascular system, they will prevent the onset of migraine attacks. There are still knowledge gaps in the role of PACAP in migraine and the risk/benefit ratio of anti-PACAP antibodies must be carefully studied
Hair testing as a marker of adherence to headache treatments
No full textBackground
Medication adherence has a critical importance in the therapy of primary headaches, both to gain pain relief and improving patients’ quality of life. Nowadays, hair is a fundamental biological specimen, alternative to the usual samples like blood and urine, to monitor adherence to pharmacological treatments: it is uninvasive and it can detect many drugs simultaneously with a detection window of many months. Therefore, in order to understandt if hair analysis should be useful to document headache patients’ adherence to chronic treatments, we analysed the detection rate of 23 therapeutic drugs in the hair of headache patients, the degree of agreement between self-reported drug and type of drug found in hair, whether the concentrations measured in hair reflected the drug doses that the patients had reported to have taken in the previous 3-month period.
Methods
93 headache patients (mean age ± SD: 48.13 ± 12.03 years; females 94%) were enrolled.
All these patients declared a chronic assumption, for at least 3 months, for headache prophylaxis or for their psychiatric comorbidities, with at least one of the following 23 drugs: alprazolam clonazepam, delorazepam diazepam, flurazepam, lorazepam, lormetazepam, triazolam, zolpidem, amitriptyline, clomipramine, citalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, mirtazapine, trazodone, levomepromazine, levosulpiride, quetiapine e topiramate.
This study was approved by the Provincial Ethical Committee of Modena and every patient gave a free-informed consent to participate the study.
A detailed pharmacological history and hair sample (7 mm diameter and 4 cm of lenght) was collected for each patient. Hair samples were analysed by liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) by a method that we developed. Statistical analysis was performed with the StataIC 13 software.
Results
All the previous 23 drugs were detected in hair samples of patients who declared them. In particular, 82% of the declared drugs were found in the 100% of samples. Negative results for the declared drugs were only 9. The agreement between type of self-reported drug and type of drug found in hair was excellent for all drugs (P<0.01, Cohen’s kappa). The relationship between the last 3 months cumulative dose and hair concentration was statistically significantly (P<0.05, linear regression analysis) for delorazepam, lorazepam, amitriptyline, citalopram, duloxetine, venlafaxine and for its metabolite, desvenlafaxine.
Conclusion
Hair appears to be a unique matrix to monitor chronic drug use in headache patients. Drugs hair concentrations are a reliable marker of adherence to headache pharmacological treatments
Glutamate receptor antagonists with the potential for migraine treatment
No full textPreclinical, clinical, and other (e.g., genetic) evidence support the concept that migraine susceptibility may at least partially result from a glutamatergic system disorder. Therefore, the receptors of the glutamatergic system are considered relatively new targets for investigational drugs to treat migraine. Investigational and established glutamate receptor antagonists (GluRAs) have been shown to possess antinociceptive properties in preclinical models of trigeminovascular nociception and have been evaluated in clinical trials. This review focuses on preclinical and clinical studies of GluRAs for the treatment of migraine. Areas covered: A PubMed database search (from 1987 to December 2016) and a review of published studies on GluRAs in migraine were conducted. Expert opinion: All published clinical trials of investigational GluRAs have been unsuccessful in establishing benefit for acute migraine treatment. Clinical trial results contrast with the preclinical data, suggesting that glutamate (Glu) does not play a decisive role after the attack has already been triggered. These antagonists may instead be useful for migraine prophylaxis. Improving patient care requires further investigating and critically analyzing the role of Glu in migraine, designing experimental models to study more receptors and their corresponding antagonists, and identifying biomarkers to facilitate trials designed to target specific subgroups of migraine patients
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Polypharmacy Among Headache Patients: A Cross-Sectional Study
Get PDFBackground
Polypharmacy can appropriately treat multiple chronic conditions, but it can also increase potential harm. Polypharmacy information for primary headaches is minimal, despite drugs being the main tools to manage headaches.
Objective
The aim was to evaluate the prevalence, characteristics and risk factors of polypharmacy in patients with primary headaches and examine whether these variables differ between episodic and chronic headache patients.
Methods
We analysed polypharmacy (simultaneous use of five or more medications), medication type, comorbidity, and risk factors in 300 patients (mean age 42.81 ± 13.21 years) with primary headaches, divided into episodic and chronic, afferent to a headache centre.
Results
Patients took an average of 4.37 medications. Polypharmacy was common in 40.7% of patients, and among chronic patients, it reached 58.8%. Most patients used medications (mainly nonsteroidal anti-inflammatory drugs; 73.5%) to treat acute headaches, and 30.4% of episodic and 64.7% of chronic sufferers underwent prophylactic treatment (P < 0.0001), mostly using antidepressants (77.3%). Up to 76.7% of the cohort was taking other medications, primarily for acid-related disorders (21.7%). Comorbidities were present in 59.7% of the cohort. Variables significantly associated with polypharmacy were comorbidities, prophylactic treatment, and triptans (P < 0.001).
Conclusions
Patients with primary headaches, mainly young adults, are exposed to high polypharmacy, comparable to that of the elderly. Because increased numbers of drugs increase the risk of adverse reactions, the many medications concomitantly taken by primary headache sufferers should be frequently reviewed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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