Evaluating the efficacy of CGRP mAbs and gepants for the preventive treatment of migraine: A systematic review and network meta-analysis of phase 3 randomised controlled trials

Migraine; PreventionMigranya; PrevencióMigraña; PrevenciónBackground Several novel treatments targeting the calcitonin gene-related peptide pathway have been developed for migraine. We evaluated the efficacy of these medications, including atogepant, rimegepant, erenumab, eptinezumab, fremanezumab, and galcanezumab, for the prevention of migraine via network meta-analysis. Methods Databases, including MEDLINE via PubMed, EMBASE, and Cochrane central, were systematically reviewed, and all eligible phase 3 randomised controlled trials were included. Results Nineteen studies (n = 14,584 participants) were included. Studies included episodic (n = 11) and chronic (n = 4) migraine or both (n = 4). All interventions, except for eptinzumab 30 mg, significantly reduced mean monthly migraine days compared to placebo. All medications had a higher ≥50% responder rate than placebo and results were statistically significant in those with the subcutaneous or intravenous route of administrations, but not with the oral one. All medications significantly reduced mean monthly headache days, although no data for this outcome was available for rimegepant, and mean monthly acute medication days, with no data for eptinezumab. Conclusion The results show that medications targeting calcitonin gene-related peptide were effective in preventing migraine compared to placebo. Considering limitations of single studies, different populations such as episodic and chronic migraine, and the absence of head-to-head trials, all novel treatments decreased mean monthly migraine and headache days, and showed higher 50%, 75% and 100% responder rates than placebo

Relationship between Vitamin D Receptor Gene Polymorphisms and Migraine without Aura in an Iranian Population

Background. Inflammation has a key role in migraine pathophysiology. Vitamin D is an effective anti-inflammatory agent. The aim of this study was to investigate the association between migraine and two vitamin D receptor (VDR) polymorphisms (TaqI and FokI) and also the relationship between VDR polymorphisms and headache severity. Methods. In this case-control study we assessed 103 patients with newly diagnosed migraine without aura and 100 healthy subjects. Patients filled headache impact test-6 (HIT-6) as a tool to assess headache severity. Results. Genotype frequencies of VDR were significantly different between control and migraine patients. Heterozygote genotypes (Ff and Tt) were statistically more frequent in the migraine patients than the control subjects both for TaqI gene ( = 0.018; OR = 1.81, 95% CI = 1.03-3.18) and FokI gene polymorphisms ( = 0.001; OR = 2.91, 95% CI = 1.47-5.77). Also f and t alleles were more frequent in the migraine patients. Total HIT-6 score was significantly different between FokI heterozygote and homozygote patients (60.32 ± 1.87 versus 49.87 ± 2.69, resp., = 0.004). Conclusions. In conclusion our results showed that TaqI and FokI gene polymorphisms are associated with migraine without aura in Iranians patients. Also headache severity in FokI heterozygote patients was significantly greater than in the homozygote patients

Novel approaches for migraine management and prevention: considering comorbidities and related disorders

Headache is the most common neurological symptom, and headache disorders are associated with considerable burden. In this thesis, I present novel approaches for headache and migraine management, considering some related disorders and associated comorbidities. Chapter 1 introduces my research and outlines my thesis. In chapter 2, I summarise non-pharmacological approaches to migraine management via a narrative review covering common migraine comorbidities, identifying triggers, lifestyle modifications, behavioural interventions, neuromodulation techniques and dietary supplements. In chapter 3, a cluster randomised clinical trial on the effects of salt reduction on headache is reported. The results showed that salt reduction did not reduce headache. The results are presented in the context of a meta-analysis, which suggests that this finding might be because the intervention did not lower diastolic blood pressure. In chapter 4, systematic reviews and meta-analysis are presented. The first of these focuses on trials of blood pressure-lowering drugs in participants with episodic migraine. And demonstrates potential benefits for all classes of blood pressure lowering medications. The second focuses on trials in a broad range of patient populations, mostly hypertension, in which headache was one of the outcomes recorded. The results show that all major classes of blood pressure lowering medications, except for calcium channel blockers, reduce headache, and that greater blood pressure reductions are associated with greater reductions in headache. In chapter 5, a systematic review and network meta-analysis showed that, new antimigraine medicines that act against calcitonin gene-related peptide are both effective and safe. However, further studies are needed to evaluate their safety in individuals with cardiovascular disorders. In chapter 6, I discuss the association between migraine and diabetes mellitus through a narrative review. The results suggest an inverse association between the two diseases in older age group. In chapter 7, I discuss the impact of Coronavirus disease on migraine and its management. Data from approximately 125,000 phone migraine app users revealed an increase in the number of headache reports from 2018 to 2020. In addition, telehealth was used more frequently during the pandemic. The current thesis highlights the importance of considering related disorders in the management of headache and migraine

Training Team’s Attitudes Toward The Patient’s Consent To Participate In Clinical Education

Introduction: In educational hospitals, sometimes the patients that seek medical health care are involved in teaching and learning process without enough knowledge about medical students’ skills. This study aimed to examine medical training team’s attitude toward patient's consent to participate in clinical training. Methods: This is a descriptive cross-sectional study conducted at Isfahan University of medical sciences using a researcher-made 12-item questionnaire with 5-point Likert Scale. From the target population including all of the professors and residents of Isfahan University of medical sciences, 61 took part in study. Results: Forty two point five percent of the participants were residents and 57.5% were professors. The overall mean attitude score was 34.9 ±3.03 that was considered moderate. The mean attitude score for professors and residents were 35.58±3.35 and 33.88 ±3.03, respectively which were not significantly different. Most of the participants believed that patients should not be informed about students' ability levels before examination. Conclusion: It seems that the concern of the medical training team about lack of patient cooperation in teaching and learning process results in ignoring in patients' rights in making an informed choice. Conducting further studies in order to find the causes and solutions to improve and upgrade the existing situation is suggested

Medical students\' Study Resources: Books or Notes

Introduction: Given the importance and impact of test resources on medical student’ learning, this study aimed to assess the time devoted to study books and notes during the semester and exam time. Methods: This descriptive-analytic study was conducted on all medical students (120) who were passing internship period at Isfahan University of medical sciences in 2011. Devoted time to study books and notes was determined. Data analysis was done using t test. Results: The mean and standard deviation of time devoted to study book for students who their mean score were above average (15.89±0.96) was 34.61±4.08. This was 23.12±5.30 for students who their mean score were less than average. It had significant difference. Conclusion: The results of this study showed that, students with lower mean score were more interested in studying notes during the semester and test time. Therefore, it is suggested to conduct further studies to investigate the study sources of students in different academic degree levels

The impact of Coronavirus disease 2019 (COVID-19) pandemic on migraine disorder.

OBJECTIVE: To evaluate the impact of the Coronavirus disease of 2019 (COVID-19) pandemic on patients with migraine. METHODS: Self-reported data from a migraine tracking smartphone application, Migraine Buddy, were used. Data were collected from users who reported at least one attack in the Jan, Feb, Mar and Apr of 2018, 2019 and 2020. In addition, a survey was conducted to evaluate the impact of COVID-19 on migraine management. RESULTS: On average, data from 124,717 users per month (mean age 36.3 +/- 10.9 years and 89% female) were collected. Overall, the mean frequency of migraine headache was higher in 2020 than in 2019 and higher in 2019 than in 2018. The four commonest headache triggers in 2018, 2019 and 2020 were stress in 39.7, 38.4 and 36.1%, lack of sleep in 25, 25 and 22.8%, neck pain, 20, 20.4 and 19.3 and anxiety in 19, 18.4 and 18.4% of participants, respectively. 1689 users participated in the survey and they reported that they preferred face-to-face (54.29%) to telehealth (11.9%) consultations. CONCLUSION: An increase in migraine frequency from 2018 to 2020 was reported by the users of the mobile phone. This could reflect a real increase or change in reporting habits. Stress, lack of sleep, neck pain and anxiety were the commonest attack triggers. The frequency of these triggers decreased slightly in 2020 compared to 2019 and 2018. An increase in telehealth consultations with specialists was reported in the survey but migraine patients preferred face-to-face consultations

Pistacia atlantica Resin Has a Dose-Dependent Effect on Angiogenesis and Skin Burn Wound Healing in Rat

Objectives. The aim of the present study was to evaluate the effect of Pistacia atlantica resin extract on the rat skin burn wound healing. Methods. Thirty-two Wistar rats were divided into four groups and treated by vehicle, 5%, 10%, and 20% concentration of Pistacia atlantica resin extract for 14 days (G1, G2, G3, and G4, resp.). The efficacy of treatment was assessed based on reduction of burn wound size and histological and molecular characteristics. Results. α-Pinene (46.57%) was the main content of essential oil of resin. There were no statistically significant differences between groups according to wound size analysis. The mean histological wound healing scores were not statistically different. Capillary counts of G2 and G3 were significantly higher than those of the G1 ( and 0.032, resp.). NO concentration in wound fluids on the 5th day of study was not significantly different between groups (). But bFGF concentration in G2 and G3 and PDGF concentration in G3 were significantly higher in comparison to G1 (, 0.017, and 0.019, resp.). Conclusion. Our results revealed that Pistacia atlantica resin extract has a concentration-dependent effect on the healing of burn wounds after 14 days of treatment by increasing the concentration of bFGF and PDGF and also through improving the angiogenesis

Relationship between Vitamin D Receptor Gene Polymorphisms and Migraine without Aura in an Iranian Population

Background. Inflammation has a key role in migraine pathophysiology. Vitamin D is an effective anti-inflammatory agent. The aim of this study was to investigate the association between migraine and two vitamin D receptor (VDR) polymorphisms (TaqI and FokI) and also the relationship between VDR polymorphisms and headache severity. Methods. In this case-control study we assessed 103 patients with newly diagnosed migraine without aura and 100 healthy subjects. Patients filled headache impact test-6 (HIT-6) as a tool to assess headache severity. Results. Genotype frequencies of VDR were significantly different between control and migraine patients. Heterozygote genotypes (Ff and Tt) were statistically more frequent in the migraine patients than the control subjects both for TaqI gene (; OR = 1.81, 95% CI = 1.03–3.18) and FokI gene polymorphisms (; OR = 2.91, 95% CI = 1.47–5.77). Also f and t alleles were more frequent in the migraine patients. Total HIT-6 score was significantly different between FokI heterozygote and homozygote patients ( versus , resp., ). Conclusions. In conclusion our results showed that TaqI and FokI gene polymorphisms are associated with migraine without aura in Iranians patients. Also headache severity in FokI heterozygote patients was significantly greater than in the homozygote patients

Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature

Background: We performed a random-effects network meta-analysis to study the efficacy and safety of newly developed drugs for the acute treatment of migraine attacks. Methods: MEDLINE via PubMed, Embase and The Cochrane Register of Controlled Trials were searched from inception to 11 February 2022. Phase 3 randomized controlled trials examining all formulations of lasmiditan, rimegepant and ubrogepant for the acute treatment of adults with migraine, were included. Data were extracted following the PRISMA guidelines. Results: Seven studies (SAMURAI, SPARTAN, CENTURION, Study 302, Study 303, ACHIEVE I and II) involving n = 12,859 patients were included. All treatments were superior in efficacy to placebo. Lasmiditan 200 mg showed the highest two-hour pain freedom, while two-hour freedom from most bothersome symptom was equally achieved by the higher doses of lasmiditan (100 and 200 mg), rimegepant and the higher doses of ubrogepant (50 and 100 mg). The odds of treatment-emergent adverse events were greatest with all doses of lasmiditan. Conclusion: Lasmiditan 200 mg was the most effective intervention in the treatment of migraine attacks, although it was associated with high degrees of dizziness, nausea and somnolence. Rimegepant showed slightly lower, but similar efficacy rates to lasmiditan. Ubrogepant had overall the best tolerability profile. These conclusions are limited by the absence of head-to-head comparisons, limitations of individual trials and of the meta-analysis methodology itself.PROSPERO trial registration: CRD42022308224

Vitamin D Status in Migraine Patients: A Case-Control Study

Background. There have been few studies on the relation between vitamin D and migraine. We investigated the prevalence of vitamin D deficiency in migraine patients and compared it with a control group. We also evaluated the relationship of vitamin D deficiency with severity of migraine. Methods. 105 newly diagnosed migraine patients and 110 controls, matched for age, sex, socioeconomic status, education, and sun exposure, were enrolled during the spring of 2011. 25-Hydroxy vitamin D [25(OH)D] plasma levels were measured by chemiluminescence immunoassay. Results. The mean ± SE concentration of 25(OH)D was 13.55±0.91 ng/mL in cases and 13.19±1.19 ng/mL in controls. There was no significant difference in 25(OH)D concentration between cases and controls. We found no relationship between severity of headache and 25(OH)D status. Conclusions. We did not find any association between migraine and vitamin D status; also, severity of headaches was not related to 25(OH)D level. Further studies with larger sample sizes are required to confirm our results