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BACKGROUND: We primarily aimed to ascertain whether treatment with OnabotulinumtoxinA (BoNTA) might influence the extent of the interictal burden and cutaneous allodynia in patients with chronic migraine (CM). METHODS: Seventy CM patients, who received three consecutive cycles of BoNTA, were studied. The interictal burden was assessed with the Migraine Interictal Burden Scale (MIBS-4), while cutaneous allodynia was examined with the Allodynia Symptom Checklist (ASC-12) together with PI-NRS VAS to obtain hair brushing scores, and then these were compared from baseline (T0) to the last efficacy evaluation follow-up (T1). Efficacy outcomes, mostly mean headache days (MHD) and "Headache Impact Test" scores, were also assessed between T0 and T1. RESULTS: BONTA improved the interictal burden, with a decrease in MIBS-4 scoring by an average of -7 at T1, compared to baseline (p < 0.001). The percentage of patients with a moderate/severe interictal burden was substantially decreased. Likewise, BoNTA reduced the extent of cutaneous allodynia, with a significant reduction in both the ASC-12 (1 vs. 6; p < 0.001) and PI-NRS VAS (1 vs. 5; p < 0.001) to hair brushing median scores at T1, compared to baseline. Reduced MHD rates were significantly associated with a smaller interictal burden at T1. The efficacy of BoNTA, with a significant reduction in MHD and HIT-6 scores at T1 compared to T0, was re-confirmed. CONCLUSIONS: BoNTA resulted in a statistically significant reduction in the interictal burden and also improved cutaneous allodynia. The reduction in ictal burden was associated with the down-scaling of the interictal burden. Hence, BoNTA improved the full spectrum of migraine impairment by diminishing the clinical expression of central sensitization.
Assuntos
Toxinas Botulínicas Tipo A , Transtornos de Enxaqueca , Humanos , Toxinas Botulínicas Tipo A/uso terapêutico , Hiperalgesia/tratamento farmacológico , Resultado do Tratamento , Transtornos de Enxaqueca/tratamento farmacológico , Cefaleia/tratamento farmacológicoRESUMO
Transposable elements (TEs) are prevalent repeats in the human genome, play a significant role in the regulome, and their disruption can contribute to tumorigenesis. However, TE influence on gene expression in cancer remains unclear. Here, we analyze 275 normal colon and 276 colorectal cancer samples from the SYSCOL cohort, discovering 10,231 and 5,199 TE-expression quantitative trait loci (eQTLs) in normal and tumor tissues, respectively, of which 376 are colorectal cancer specific eQTLs, likely due to methylation changes. Tumor-specific TE-eQTLs show greater enrichment of transcription factors, compared to shared TE-eQTLs suggesting specific regulation of their expression in tumor. Bayesian networks reveal 1,766 TEs as mediators of genetic effects, altering the expression of 1,558 genes, including 55 known cancer driver genes and show that tumor-specific TE-eQTLs trigger the driver capability of TEs. These insights expand our knowledge of cancer drivers, deepening our understanding of tumorigenesis and presenting potential avenues for therapeutic interventions.
Assuntos
Neoplasias Colorretais , Elementos de DNA Transponíveis , Humanos , Elementos de DNA Transponíveis/genética , Teorema de Bayes , Fatores de Transcrição/metabolismo , Carcinogênese/genética , Neoplasias Colorretais/genéticaRESUMO
Objective: Phase II/III randomized clinical trials (RCTs) are vulnerable to many types of bias beyond randomization. Insights into the reporting quality of RCTs involving migraine patients treated with monoclonal antibodies targeting the calcitonin gene-related peptide system (anti-CGRP MAbs) are currently lacking. Our aim was to analyze the reporting quality of phase II/III RCTs involving migraine patients treated with anti-CGRP MAbs. Methods: A systematic search was performed on the PubMed and EMBASE databases, according to PRISMA guidelines, for relevant RCTs in either episodic or chronic migraine prevention. Additionally, an adapted version of the 2010 CONSORT statement checklist was utilized. The ROBvis online tool was used to document the risk of bias. Results: From the initially identified 179 articles, we finally found 31 RCTs that were eligible for evaluation. The average CONSORT compliance was 88.7% (69.7-100%), while 93.5% (N = 29) of the articles had a compliance greater than 75%. Twenty-eight CONSORT items were reported in more than 75% of the articles. The average compliance of the analyzed RCTs was 93.9% for Galcanezumab, 91.3% for Fremanezumab, followed by 85.4% for Erenumab and Eptinezumab studies. Implementation of the ROB2 tool showed some concerning "missing information" arising from the inadequate reporting. Specifically, 50% of the studies (N = 16) were categorized as having inadequate information regarding the randomization process. Conclusions: Adequate reporting quality was disclosed in the evaluated RCTs with anti-CGRP MAbs in migraine prevention. However, some methodological issues need to be highlighted to be addressed in future studies assessing the efficacy of new molecules targeting CGRP or other candidate pathways implicated in migraine pathophysiology.
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Objective: To investigate whether the incidence of triggers, prodromal symptoms, hypersensitivity symptoms accompanying headache and responses to triptans were modified during a continuous 9-month fremanezumab therapy for migraine prophylaxis. Patients and methods: We studied 63 patients with high-frequency episodic migraine (HFEM). Enrolled patients received fremanezumab for nine consecutive months before defining the response rates and being stratified into treatment responders (≥50-74% reduction in monthly headache days (MHDs)), super responders (≥75%), partial non-responders (<50%) and super non-responders (<30%). Through headache diaries, patients provided data in order to document the impact of fremanezumab on the incidence of triggers, associated symptoms followed by headache and response to triptans (the use of the migraine treatment optimization questionnaire-4 (mTOQ-4)) during the 9-month treatment period. Results: Fremanezumab had early (after 3 monthly cycles) beneficial effects on the response to triptans in the majority of responders with relevant increases in mTOQ-4 scoring, but also in half of partial non-responders. A significant reduction in median days with migraine-associated symptoms was seen in responders after 6 months of therapy with fremanezumab, mostly for osmophobia, photophobia, phonophobia and nausea/vomiting, but partial non-responders also benefited. Likewise, the incidence of self-reported prodromal symptoms was significantly reduced in responders and was modestly diminished in partial non-responders. Triggers remained unaffected in both responders and non-responders. Conclusions: Fremanezumab given for at least 6-9 months may exert neuromodulatory effects in the migraine brain. These effects could result both in the inhibition of migraine chronification, but also in the diminishing of the magnitude of migraine-associated symptoms, mostly in responders and in partial non-responders.
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Objective: The Greek Society of Migraine and Headache Patients conducted its third in-line population web-based survey in 2023 to ascertain if the burden of the disease and the patients' satisfaction with conventional and novel migraine therapies are changing compared to our previous findings from 2018 and 2020. Methods: The sampling process was based on a random call to participants to reply to a specific migraine-focused self-administered questionnaire, including 83 questions in Greek, which was distributed nationwide through the online research software SurveyMonkey. Results: We eventually enrolled 2565 patients, the majority of which were females. Our findings clearly demonstrate that migraine is still a burdensome condition. The degree of its impact on all aspects of productivity depends on the monthly frequency of migraine and the response rates to acute and prophylactic treatments. A total of 1029 (42.4%) of the patients had visited the emergency room mainly for unresponsiveness to acute treatments or aura-related symptoms. Triptans seem to be partly effective as acute therapies. OnabotulinumtoxinA seems to be effective for almost half of chronic migraine patients (43.9%) to report adequate satisfaction with this treatment (27.8% were "fairly happy", 10.6% were "very happy", and 5.5% were "extremely happy"). Due to their high rates of preventative effectiveness, most respondents treated with anti-CGRP Mabs expressed their optimism concerning their future while living with their migraine (88.25%), as well as towards further improvements in their quality of life (82.8%) status, mostly with fremanezumab. Conclusions: The patients recognize the usefulness of anti-CGRP Mabs in migraine prevention and consequently seem to be more optimistic than before about living with migraine. Considering the market change that is anticipated with the use of gepants and ditans, larger longitudinal population-based studies are warranted to further explore if the new era of migraine therapeutics might further lessen the burden of the disease.
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BACKGROUND: To identify the preferences and perceptions of migraine patients for acute and preventive treatment options and to investigate which treatment outcomes are the most important. DESIGN AND METHODS: The authors performed a choice-format survey in a cohort of migraine patients from Greece and Cyprus. A self-administered questionnaire developed in collaboration with the Greek Society of Migraine Patients was used. RESULTS: Questionnaires were collected from 617 migraine patients. Efficacy was preferred over safety as the single most important parameter, both in acute and preventive treatment. When analyzing single outcomes, patients prioritized a complete pain remission at 1-hour post-dose for acute therapies. Regarding migraine prevention, a 75% reduction in frequency, intensity of pain, accompanying symptoms and acute medication intake were considered as most important. Conversely, outcomes routinely used in clinical trials, namely complete or partial pain remission at 2-hours post-dose for acute treatment and 50% or 30% reduction in migraine frequency for prevention, were not deemed particularly relevant. Tablet formulation was mostly preferred, both in acute and preventive treatment. Conclusion: Listening to patients' needs may add a piece of the puzzle that is generally missing in clinical practice and often explains the lack of adherence in both acute and preventative anti-migraine therapies.