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Introduction: Migraine, a debilitating neurological disorder characterized by recurrent headaches, affects over 1.1 billion individuals globally. Diabetes mellitus (DM), a chronic metabolic condition marked by high blood sugar levels, affects 463 million individuals according to the International Diabetes Federation. Our study aimed to evaluate the association between migraine and DM and to identify several demographic, socioeconomic, and lifestyle factors, as well as medical and psychiatric comorbidities, associated with migraine among individuals with DM. Methods: This cross-sectional study is based on data from the European Health Interview Surveys conducted in 2009, 2014, and 2019 in Hungary. Pearson's chisquared tests and multiple logistic regression models were used to assess associations. Statistical significance was set at p<0.05. Results: In multiple regression analyses, we found no significant association between DM and migraine after adjusting for socioeconomic status, various health conditions, and lifestyle factors (OR=0.84, 95% CI: 0.66-1.06). However, adults with DM who had comorbid conditions including stroke (OR=2.08, 95% CI: 1.06-4.08), low back pain (OR=3.52, 95% CI: 2.13-5.84), and depression (OR=4.91, 95% CI: 2.84-8.47) were significantly more likely to suffer from migraine. Discussion: Our study found no significant difference in the prevalence of migraine among adults with and without diabetes mellitus. However, several comorbidities were found to be significantly associated with migraine occurrence in those with DM. Thus, the study's results highlight the need for proper management of diabetes, especially in terms of comorbidities, to mitigate migraine risk factors and improve patient outcomes. [ABSTRACT FROM AUTHOR]

A single-blind, randomized controlled trial comparing oxycodone and fentanyl for patient-controlled intravenous analgesia (PCIA) after laparoscopic hysteromyomectomy found comparable pain relief between the two groups. The study included 60 participants, with NRS scores for pain at rest and when moving showing no significant differences between oxycodone and fentanyl groups at various time points postoperatively. Self-rating depression scale scores were also similar between the groups at 48 h. However, patients' satisfaction with PCIA was higher in the oxycodone group, with 73.3% reporting being very satisfied compared to 36.7% in the fentanyl group. Additionally, the oxycodone group had fewer incidences of headaches within 48 h postoperatively compared to the fentanyl group. These findings suggest that oxycodone may offer comparable pain relief, higher patient satisfaction, and fewer headaches for patients undergoing laparoscopic hysteromyomectomy compared to fentanyl, making it a suitable option for postoperative pain management in this population. Clinical trial registration number The study was registered with CHICTR.org, ChiCTR2100051924. [ABSTRACT FROM AUTHOR]

Introduction: Glucagon-like peptide-1 receptor agonist use has increased over the last decade for glycemic control in type 2 diabetes mellitus, cardiovascular risk reduction, and weight loss. Clinical trials indicate that gastrointestinal adverse effects are commonly experienced and severe hypoglycemia is rare; however, there is little data regarding glucagon-like peptide-1 receptor agonist in overdose. Methods: We performed a retrospective chart review evaluating and characterizing glucagon-like peptide-1 receptor agonist exposures reported to a single poison center between 2006 and 2023. Patient demographics, circumstances of exposure, clinical effects, and outcomes were abstracted from charts. Descriptive statistics were utilized to summarize demographic information and clinical factor data. Results: A total of 152 charts met inclusion criteria. Therapeutic errors accounted for 91% of exposures. Most patients (67%) reported no symptoms, although not all patients were followed to a definitive outcome. Nausea, vomiting, generalized weakness, and abdominal pain were the predominant symptoms reported. Most patients (62%) were monitored and closely followed in the home setting. Hypoglycemia was rare but occurred in the setting of a single agent glucagon-like peptide-1 receptor agonist exposure in two patients. Two additional patients who developed hypoglycemia involved co-administration of insulin. 21% of the exposures were related to errors on initial use of the pen. Conclusion: Exposures to glucagon-like peptide-1 receptor agonist have increased substantially over the years. Effects from an exposure tended to be mild and primarily involve gastrointestinal symptoms. Hypoglycemia was rare. Therapeutic and administration errors were common. Education on pen administration may help to reduce errors. [ABSTRACT FROM AUTHOR]

In the diagnosis of migraine, which is a neurovascular disease, gadolinium-based contrast agents (GBCAs) are used to rule out more serious conditions. On the other hand, it remains unclear as a scientific gap whether GBCAs may trigger migraine-related pain. The aim of this study was to investigate the effect of GBCAs on mechanical and thermal pain behaviour in a nitroglycerin (NTG)-induced migraine model in mice. NTG (10 mg/kg) was administered intraperitoneally to adult (6–8 weeks old) BALB/c mice 2 h before behavioral tests 5 times every other day on days 1st, 3rd, 5th and 9th to induce migraine model (N = 50). As GBCAs, gadobenate dimeglumine (linear-ionic), Gadodiamide (linear-nonionic), and gadobutrol (macrocyclic-nonionic) were delivered intravenously through the tail vein of mice for 5 days on test days. Mechanical pain threshold (plantar and facial withdrawal threshold) was evaluated by plantar von Frey and periorbital von Frey tests on days 1st, 5th, and 9th, and thermal pain threshold (latency) was evaluated by hot plate and cold plate tests on days 3rd and 7th. There was a statistically significant increase in mechanical and thermal hyperalgesia in NTG administered groups compared to the control group. Gadodiamide, gadobutrol and gadobenate dimeglumine administration significantly decreased latency, paw and facial withdrawal threshold (0.18 ± 0.05, 0.17 ± 0.07, 0.16 ± 0.09; 9th day values respectively) compared to NTG group (0.27 ± 0.05). The results of this in vivo study show that GBCAs produce effects that may trigger migraine attacks in migraine. It is recommended that these effects be further investigated and supported by further clinical studies. [ABSTRACT FROM AUTHOR]

Chronic orofacial pain disorders are common debilitating conditions, affecting the trigeminal system. Its underlying pathophysiological mechanisms are still unclear and the therapy is often unsatisfactory, therefore, preclinical models are crucial to identify the key mediators and novel treatment options. Complete Freund's adjuvant (CFA)-induced orofacial inflammatory allodynia/hyperalgesia is commonly used in rodents, but it has not been validated with currently used drugs. Here we tested the effects of the adjuvant analgesic/antiepileptic voltage-gated Na+ channel blocker complex mechanism of action topiramate in comparison with the gold standard antimigraine serotonin 5-HT1B/D receptor agonist sumatriptan in this model. CFA was injected subcutaneously into the right whisker pad of male Sprague-Dawley rats (250-300 g), then mechanonociceptive threshold values were investigated with von Frey filaments (3, 5, and 7 days after CFA injection). Effects of topiramate (30 mg/kg per os) and sumatriptan (1 mg/kg subcutaneous) on the adjuvant-induced chronic inflammatory orofacial allodynia were investigated 60, 120, and 180 min after the treatments each day. To determine the optimal concentration for drug effect analysis, we tested the effects of two different CFA-concentrations (1 and 0.5 mg/mL) on mechanonociceptive thresholds. Both concentrations of CFA induced a chronic orofacial allodynia in 60% of all rats. Although, higher CFA concentration induced greater allodynia, much more stable threshold reduction was observed with the lower CFA concentration: on day 3 the thresholds decreased from 18.30 g to approximately 11 g (low) and 5 g (high), respectively, however a slight increase was observed in the case of higher CFA concentration (on days 5, 7, and 11). In all investigation days, topiramate showed significant anti-allodynic effect comparing the pre and post drug dose and comparing the vehicle treated to the drug treated groups. Sumatriptan also caused a significant threshold increase compared to pre dose thresholds (day 3) and also showed a slight anti-allodynic effect compared to the vehicle-treated group (day 3 and 5). In the present study CFA-induced chronic orofacial allodynia was reversed by topiramate in rats validating the model with the adjuvant analgesic. Other than establishing a validated orofacial pain-related syndrome model in rats, new ways are opened for the repurposing of topiramate. [ABSTRACT FROM AUTHOR]

Background: Diverse studies have revealed discrepant evidence concerning the causal association between Corona Virus Disease 2019 (COVID-19) and COVID-19 vaccination in relation to migraines. Investigating the correlation between the former two factors and migraines can facilitate policymakers in the precise formulation of comprehensive post-pandemic interventions while urging the populace to adopt a judicious perspective on COVID-19 vaccination. Methods: We undertook a Mendelian randomization (MR) study. The primary assessment of the causal relationship between the three different COVID-19 exposures and migraine was conducted using the standard inverse variance weighted (IVW) approach. In the supplementary analysis, we also employed two methodologies: the weighted median estimator (WME) and the MR-Egger regression. Ultimately, the reliability and stability of the outcomes were assessed via Cochran's Q test, the leave-one-out method, the MR-Egger intercept test, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. Results: The results indicate an absence of correlation between genetically predicted COVID-19 (①Very severe respiratory confirmed COVID-19: odds ratio [OR], 1.0000881; 95%CI, 0.999748–1.000428; p = 0.6118; ②Hospitalized COVID-19: OR, 1.000024; 95%CI, 0.9994893–1.000559; p = 0.931;③SARS-CoV-2 infection: OR, 1.000358; 95%CI, 0.999023–1.001695; p = 0.5993) and the risk of migraine. Furthermore, the MR-Egger regression and WME also yielded no evidence of COVID-19 elevating the risk of migraine occurrence. Sensitivity analysis affirmed the robustness and consistency of all outcomes. Conclusions: The results of this study do not offer genetic evidence to substantiate a causal relationship between COVID-19 and migraines. Thus, the deduction drawn from COVID-19 genetic data is that COVID-19 vaccination is unlikely to exert an impact on the occurrence of migraines, though this conclusion warrants further investigation. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions Our primary outcome was to determine the feasibility of patients with post‐traumatic headache (PTH) keeping a daily headache diary and using sumatriptan as directed. Secondary outcomes include determining if sumatriptan is effective in aborting PTH and whether headache resolution is dependent on PTH phenotype.PTH is prevalent and persistent after traumatic brain injury, yet there have been few studies evaluating the effects of pharmacological treatments in individuals with PTH.This is a single‐arm, prospective, non‐randomized phase 2 clinical trial registered at Clinicaltrials.gov (NCT01854385) and conducted from 2013 to 2017. Data analysis was completed in 2022. Of the 299 participants screened, 40 were enrolled in the study. Participants kept a headache diary documenting headache characteristics and severity. Headache characteristics were used to determine PTH phenotypes of migraine‐like, probable migraine‐like, or non‐migraine‐like. Participants reported whether sumatriptan was used for their headache, their response to the medication, if a second dose was taken, and their response to the second dose.A total of 15 participants out of the 40 enrolled (mean [SD] age, 41.9 [14.2] years, and 53% [21/40] male), met the criteria for the use of sumatriptan, and completed all assessments. Average headache diary compliance rate for the final month of the study was 80% (372/465). While sumatriptan was used for only 19% (122/654) of all reported headaches, 72% (88/122) of those headaches resolved within 2 h of taking the medication. Resolution of headaches with sumatriptan was not significantly different among headache phenotypes (migraine‐like: 22/38 [58%], probable migraine‐like: 24/29 [83%], non‐migraine‐like: 6/15 [40%]; p = 0.154).A daily headache diary is feasible for tracking headache symptoms. Preliminary results also suggest that sumatriptan, a migraine‐specific medication, may be beneficial for the treatment of PTH of different clinical phenotypes. Future studies, such as a phase 3 clinical trial with a larger sample size, are needed to better understand the efficacy of sumatriptan in the treatment of PTH. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the real-world profile of adverse events (AEs) associated with gepant medications in the clinical treatment of migraines by analyzing data collected from the VigiAccess database and the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. As novel migraine therapies, gepants act by targeting the calcitonin gene-related peptide (CGRP) pathway, demonstrating effective control of migraine attacks and good tolerability. Nonetheless, comprehensive realworld studies on the safety of gepants are still lacking, particularly regarding their safety in large populations, long-term use, and potential adverse reactions in specific groups, which necessitates further empirical research. Leveraging these two international adverse event reporting system databases, we systematically gathered and analyzed reports of AEs related to gepant medications, such as rimegepant. Our focus encompasses but is not limited to severe, new, and rare adverse reactions induced by the drugs, as well as safety issues pertaining to the gastrointestinal, cardiovascular, hepatic, and renal systems. Through descriptive statistical analyses, we assessed the incidence and characteristics of AEs, compared AEs among gepants, and uncovered previously unknown AE information, all with the goal of providing a reference for the selection of clinical treatment regimens and AE monitoring. Methods: By extracting all AE reports concerning "rimegepant", "atogepant", and "ubrogepant" from the VigiAccess and FAERS database since its establishment up to 31 March 2024, a retrospective quantitative analysis was conducted. The reporting odds ratio (ROR) method were used to compare AEs among the three gepants. Results: In the VigiAccess and FAERS databases, 23542 AE reports in total, respectively, were identified as being related to gepant medications. Among gastrointestinal system AEs, rimegepant had the greatest proportion and greatest signal strength; nausea was most severe and had the strongest signal in rimegepant AEs, whereas constipation was most prominent and had the strongest signal in atogepant AEs. In skin and subcutaneous tissue disorders, rash and pruritus were more frequently observed with rimegepant, followed by ubrogepant. Alopecia emerged as a novel AE, being more severe in rimegepant and secondarily in atogepant. Regarding cardiac disorders, the three gepants showed comparable rates of cardiac AEs, yet rimegepant exhibited the strongest AE signal. In musculoskeletal and connective tissue AEs, ubrogepant presented the most positive signals for skeletal muscle AEs. Furthermore, among the rare blood and lymphatic system disorder AEs, rimegepant had the highest number of reports of Raynaud's phenomenon and the strongest signal. The study also revealed that while reports of AEs involving liver diseases were scarce across the three gepants, severe AEs were detected in clinical trials, highlighting the need for continued, enhanced monitoring of liver system AEs through large-scale datasets. Conclusion: Gepant medications exhibit similarities and differences in their safety profiles. Analysis of the two databases indicated the presence of AEs across various systems, including gastrointestinal disorders, skin and subcutaneous tissue diseases, musculoskeletal and connective tissue disorders, organ-specific effects, and liver diseases. However, each drug displays distinct incidences and signal intensities for these AEs. Additionally, the study revealed a rare AE in the form of Raynaud's phenomenon. These findings suggest that during clinical use, individualized medication selection and AE monitoring should be based on the patient's physiological condition and specific characteristics. [ABSTRACT FROM AUTHOR]

Background: Migraine and dizziness often coexist, with vestibular migraine (VM) presenting with vestibular symptoms and headaches. Calcitonin gene-related peptide (CGRP) may be involved in motion-induced symptoms; however, studies on the use of anti-CGRP monoclonal antibodies (mAbs) for the treatment of VM have yielded conflicting results. This study aimed to clarify the effectiveness of anti-CGRP mAbs in VM treatment. Methods: This retrospective observational cohort study, conducted between 1 January 2021 and 31 March 2023, assessed 12 Japanese patients with VM who were treated with anti-CGRP mAbs (CGRP group) for 6 months and 11 Japanese patients who received standard of care for VM and served as controls. Clinical questionnaires and equilibrium tests were administered, with primary outcomes including changes in Dizziness Handicap Inventory (DHI) scores compared with baseline values. Objective variables included the DHI score and explanatory variables included demographic data, balance test results, head-up tilt (HUT) test results, vestibular test results and questionnaire survey results. Analysis of variance was used to assess the treatment effects of anti-CGRP mAbs, and multivariate regression analysis was performed to identify mAb responders. Results: After 6 months, the CGRP group showed significant improvements in DHI scores [0 versus 6 months, odds ratio (95% confidence interval): 22.01 (0.13–43.88)] and number of vertigo/dizziness attacks per month [0 versus 6 months: 10.28 (2.80–17.76)]. No significant difference was observed in the control group [DHI scores, 0 versus 6 months: 0.65 (−26.84 to 28.14); number of vertigo/dizziness attacks per month, 0 versus 6 months: − 8.07 (− 23.77 to 7.62)]. Multivariate regression analysis showed that autonomic function at baseline was associated with mAb response in patients [β estimates (95% confidence interval): 3.63 (0.21–7.06)]. Conclusions: Treatment with anti-CGRP mAbs was more effective than conventional treatment in preventing migraine in patients with VM. While the identified factors associated with treatment responsiveness offer valuable insights into personalised treatment approaches, further prospective studies are warranted to validate the findings due to our study's retrospective design and limited sample size. [ABSTRACT FROM AUTHOR]

Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are novel high-cost treatments for the prevention of migraine. This study presents data on utilization, expenditure, and treatment patterns with CGRP mAbs available under a managed access protocol in Ireland, to a cohort of treatment refractory patients (failed 3 or more previous treatments) with chronic migraine. Data were extracted from the Primary Care Reimbursement Service High Tech claims database and special drug request online system and analyzed using Microsoft Excel and SAS. Treatment persistence was evaluated by refill patterns, and adherence was evaluated using the proportion of days covered method. Expenditure data were extracted directly from the database. Between September 1, 2021 and April 30, 2023, 1517 applications for reimbursement approval for a CGRP mAb were received; 1458 (96.1%) were approved for reimbursement. Total expenditure on CGRP mAbs in year 1 (September 1, 2021 to August 31, 2022) was €3.2 million. The majority of patients initiated treatment with fremanezumab (60.8%) or erenumab (37.1%). Almost 90% of patients were considered adherent, and treatment persistence was high, with more than 75% of patients receiving more than 12 months of treatment in our 18-month study time frame. This study demonstrates the importance of active health technology management, after reimbursement, in enabling cost-effective use of high-cost treatments while providing budget certainty for the healthcare payer. High levels of adherence and persistence suggest that treatment is successfully targeted in situations which unmet clinical need is greatest. • Calcitonin gene-related peptide monoclonal antibodies are novel, high-cost treatments for the prevention of migraine. • In 1 year of reimbursement in Ireland, the total expenditure on calcitonin gene-related peptide was €3.2 million, with the majority of approved patients being highly treatment adherent. • Health technology management can ensure cost containment while maintaining access to treatment in situations which unmet clinical need is greatest. [ABSTRACT FROM AUTHOR]

Background: Evidence regarding the best antibiotic regimen and the route of administration to treat acute focal bacterial nephritis (AFBN) is scarce. The aim of the present study was to compare the effectiveness of intravenous (IV) β-lactam antibiotics versus oral quinolones. Methods: This is a retrospective single centre study of patients diagnosed with AFBN between January 2017 and December 2018 in Hospital Universitari Vall d'Hebron, Barcelona (Spain). Patients were identified from the diagnostic codifications database. Patients treated with oral quinolones were compared with those treated with IV β-lactam antibiotics. Therapeutic failure was defined as death, relapse, or evolution to abscess within the first 30 days. Results: A total of 264 patients fulfilled the inclusion criteria. Of those, 103 patients (39%) received oral ciprofloxacin, and 70 (26.5%) IV β-lactam. The most common isolated microorganism was Escherichia coli (149, 73.8%) followed by Klebsiella pneumoniae (26, 12.9%). Mean duration of treatment was 21.3 days (SD 7.9). There were no statistical differences regarding therapeutic failure between oral quinolones and IV β-lactam treatment (6.6% vs. 8.7%, p = 0.6). Out of the 66 patients treated with intravenous antibiotics, 4 (6.1%) experienced an episode of phlebitis and 1 patient (1.5%) an episode of catheter-related bacteraemia. Conclusions: When susceptible, treatment of AFBN with oral quinolones is as effective as IV β-lactam treatment with fewer adverse events. [ABSTRACT FROM AUTHOR]

The use of haloperidol in pain management has been a topic of interest for several decades. Haloperidol is a widely used antipsychotic medication with unique pharmacologic properties that make it a potential candidate for pain management. However, the efficacy and safety of haloperidol for pain management remain controversial. This narrative review provides a summary of the current literature on the use of haloperidol for pain management, including its pharmacology, clinical effectiveness, adverse effects, and dosing regimens. We performed a comprehensive search of the literature for this review. The most robust clinical data from the past decade suggest that haloperidol has good efficacy in the treatment of pain related to gastroparesis and migraines and has shown promise for opioid use reduction in patients with chronic pain or receiving palliative care. The overall side effect profile is excellent, with zero reported events of QT-related cardiac arrest and minimal reports of sedation and transient extrapyramidal effects such as akathisia. Dosing regimens used were heterogeneous, with most ranging from 1 to 5 mg per dose via intravenous, intramuscular, or oral route. Studies with designs that isolated the effects of haloperidol from combinations of other drugs were extremely limited. Further high-quality prospective studies are needed to determine the ideal role of haloperidol in the routine clinical management of painful conditions. [ABSTRACT FROM AUTHOR]

Our sensory adaptation to cold and chemically induced coolness is mediated by the intrinsic property of TRPM8 channels to desensitize. TRPM8 is also implicated in cold-evoked pain disorders and migraine, highlighting its inhibitors as an avenue for pain relief. Despite the importance, the mechanisms of TRPM8 desensitization and inhibition remained unclear. We found, using cryo-electron microscopy, electrophysiology, and molecular dynamics simulations, that TRPM8 inhibitors bind selectively to the desensitized state of the channel. These inhibitors were used to reveal the overlapping mechanisms of desensitization and inhibition and that cold and cooling agonists share a common desensitization pathway. Furthermore, we identified the structural determinants crucial for the conformational change in TRPM8 desensitization. Our study illustrates how receptor-level conformational changes alter cold sensation, providing insights into therapeutic development. [ABSTRACT FROM AUTHOR]

Around 91% of migraine patients use over-the-counter medicines to treat attacks, often without further treatment or medical consultation. This therapeutic principle is established in most countries, regardless of how the healthcare system is otherwise structured or financed. Using Germany as an example, the basis for an expansion of attack therapy with rizatriptan as an over-the-counter triptan is described. To achieve the best possible tolerability and safety in the context of self-medication, the lowest possible dose should be selected to provide the most favourable tolerability and safety profile in the context of self-medication through low dosages. The lowest approved dose of rizatriptan is 5 mg. This was investigated in three randomized controlled trials with 752 patients. The results show that rizatriptan at a dose of 5 mg is more effective than the triptans naratriptan 2.5 mg, almotriptan 12.5 mg and sumatriptan 50 mg, which were previously available for self-medication in Germany. There was no significant difference in the frequency of adverse events with rizatriptan 5 mg compared to placebo. Rizatriptan 5 mg does not have a higher side effect potential than sumatriptan 50 mg, which is already exempt from the prescription requirement. The reasons given show that rizatriptan in a dose of 5 mg for the treatment of acute migraine attacks fulfils the requirements for a transfer from prescription to pharmacy-only status at least as well as sumatriptan 50 mg, naratriptan 2.5 mg and almotriptan 12.5 mg. From a clinical care perspective, it is desirable for affected patients to have other options available for self-medication. Non-responders to other substances also have a further treatment option with rizatriptan 5 mg, with the same or even better risk–benefit profile, to treat migraine attacks safely, effectively and in a tolerable manner as part of self-medication. [ABSTRACT FROM AUTHOR]

Rationale: Reducing the risk of exacerbation is a fundamental goal in managing stable chronic obstructive pulmonary disease (COPD). Guidelines recommend triple therapy (inhaled corticosteroids, long-acting muscarinic antagonists, and long-acting β-agonists) only as a stepup from dual therapy (long-acting muscarinic antagonists and long-acting β-agonists) for patients at continued high risk of exacerbation, because of the trade-off of an increased risk of pneumonia associated with inhaled corticosteroid–containing therapies. However, there is little evidence on the optimum timing of initiating triple therapy. Objectives: To perform a benefit–harm analysis to evaluate the net benefit of earlier initiation of triple therapy for the prevention of acute exacerbations in patients with COPD compared with standard timing recommended in current guidelines. Methods: We used a validated whole-disease microsimulation model of COPD in the Canadian general population aged ⩾40 years to determine the benefit versus harm of earlier initiation of triple therapy over a 20-year time horizon compared with standard care. We assessed net change in quality-adjusted life-years (QALYs) from the reduction in risk of acute exacerbations and the increased risk of treatment-related pneumonia in subgroups of patients with COPD defined by exacerbation history, symptoms, and disease severity. Model parameters were determined from clinical trials and other published literature. Key parameters were varied in one-way sensitivity analysis. Results: In patients at high risk of acute exacerbation (54.7% female; mean age, 74.0 yr; 68% Global Initiative for Chronic Obstructive Lung Disease grades I and II), earlier initiation of triple therapy was associated with a net QALY gain of 4.8 per 100 patients with COPD over 20 years compared with standard care. The net QALY gain increased to 5.9 per 100 patients in the subgroup of patients with a high symptom burden (modified Medical Research Council dyspnea scale score, >1). Earlier initiation remained net beneficial in all subgroup and sensitivity analysis scenarios. Conclusions: Modeling suggests that earlier initiation of triple therapy is likely to be net beneficial for patients at high risk of acute exacerbation, with an even greater benefit to patients with a high symptom burden. Further clinical research is needed to verify these findings in empirical studies. [ABSTRACT FROM AUTHOR]

Objective: Closure surgery of patent foramen ovale (PFO) has been found to effectively control cryptogenic stroke and migraine, but it is uncertain whether PFO closure could also alleviate epileptic seizures. This study aims to observe the therapeutic effect of PFO closure on epileptic seizures. Methods: Since July 11th, 2017, in the neurology department of West China Hospital, Sichuan University, Chengdu, we have been regularly monitoring patients with epilepsy who have undergone PFO closure. The patient's clinical information, such as frequency, duration, and severity of seizures, before and after surgery was recorded in detail as well as postoperative safety events. Results: Of the 31 epilepsy patients who confirmed PFO observed (27 cases were drug‐resistant epilepsy, 87.10%), average age of surgery was 23.74 years, and 12 cases were female (38.71%). After one‐year follow‐up, 26 patients (83.87%) achieved remission of seizure frequency, and 22 of whom (70.97%) experienced a remission of more than 50%. Additionally, compared to before surgery, 22 cases (70.97%) reported a decrease in the average seizure duration, and 20 cases (64.52%) reported a reduction in seizure severity. In the seizure indicators of frequency, average duration and severity, significant differences were identified between preoperative and postoperative comparisons with all test p values were <0.05. Furthermore, no serious safety events were reported except for one patient who briefly reported chest pain, and all patients expressed effective PFO closure. Significance: The PFO closure has been shown for the first time to result in a significant reduction in the frequency, duration, and severity of seizures. Patients with drug‐resistant epilepsy and PFO with a large shunt are ideal candidates for undergoing PFO closure. Plain Language Summary: Since PFO closure was found to have a good therapeutic effect on cryptogenic stroke and migraine, it has become a credible complementary therapy for the treatment of neurological diseases, and drug‐resistant epilepsy with PFO is expected to become the next target disease that PFO closure could significantly improve. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of migraine headache is higher in women. Low barometric pressure is a factor in headache triggering, but sex-related differences have not been identified. The purpose of this study was to examine sex-related differences in headache triggered by low barometric pressure. Methods: Study subjects aged 20–49 years were randomly selected from a research company's (Macromill, Inc.) web panel. Those with chronic migraine or tension-type headache invited to complete a web-based self-administered questionnaire. Logistic regression analysis was performed with the objective variable as the Headache Impact Test-6 (HIT-6) high scores (56 or more) or headache triggered by low barometric pressure. Results: Participants were 332 women and 337 men in the headache population. HIT-6 high scores were associated with age at headache occurrence 20 years or younger (OR: odds ratio 1.85, 95% CI: confidence interval 1.15–2.99, p = 0.012) and headache triggered by low barometric pressure (OR 2.11, 95%CI 1.51–2.94, p < 0.001). Headache triggered by low barometric pressure was significantly associated with women (OR 2.92, 95%CI 2.12–4.02, p < 0.001). Conclusions: Headache triggered by low barometric pressure were related to sex-related differences. It was suggested that a sex-specific treatment approach for headache triggering is needed. [ABSTRACT FROM AUTHOR]

Nandina domestica: Thunb. is a traditional Chinese herbal drug that has long been used in China and Japan for the treatment of colds, fevers, asthma, chronic bronchitis, conjunctivitis, whooping cough, pharyngeal tumors, etc. Published data have reported at least 366 constituents from N. domestica, including alkaloids, flavonoids, lignans, terpenoids, phenolic acids and their derivatives, fatty acids, and others. Of these, the isoquinoline alkaloids are considered characteristic markers for N. domestica. These alkaloids also showed the most promising bioactivities. The crude extracts or semi-purified constituents of N. domestica exhibit a variety of activities, including antitumor, dermatological, antiinflammatory, antioxidant, antimicrobial, and detoxification activities, as well as effects on respiratory system, etc. The fruit is considered poisonous when eaten raw, with nausea, vomiting, diarrhea, and abdominal pain as side effects after ingestion. Most traditional uses are supported by biological activities demonstrated in modern experimental studies, suggesting a potential medicinal value of N. domestica. However, more information is needed on its mechanisms of activity, pharmacokinetic profile of the constituents, and its safety and efficacy profile in humans. [ABSTRACT FROM AUTHOR]

Acute coronary syndrome (ACS) is a predominant cause of mortality, and the prompt and precise identification of this condition is crucial to minimize its impact. Recent research indicates that gut microbiota is associated with the onset, progression, and treatment of ACS. To investigate its role, we sequenced the gut microbiota of 38 ACS patients before and after percutaneous coronary intervention and statin therapy at three time points, examining differential species and metabolic pathways. We observed a decrease in the abundance of Parabacteroides, Escherichia, and Blautia in patients after treatment and an increase in the abundance of Gemalla, Klebsiella variicola, Klebsiella pneumoniae, and others. Two pathways related to sugar degradation were more abundant in patients before treatment, possibly correlated with disorders of sugar metabolism and risk factors, such as hyperglycemia, insulin resistance, and insufficient insulin secretion. Additionally, seven pathways related to the biosynthesis of vitamin K2 and its homolog were reduced after treatment, suggesting that ACS patients may gradually recover after therapy. The gut microbiota of patients treated with different statins exhibited notable differences after treatment. Rosuvastatin appeared to promote the growth of anti-inflammatory bacteria while reducing pro-inflammatory bacteria, whereas atorvastatin may have mixed effects on pro-inflammatory and anti-inflammatory bacteria while increasing the abundance of Bacteroides. Our research will provide valuable insights and enhance comprehension of ACS, leading to better patient diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Due to more frequent and intense attacks, chronic migraine (CM) sufferers usually report more disability compared to patients with episodic migraine (EM). There is increasing evidence that points to inflammatory diet and lifestyle as a probable underlying cause of migraine. The present study investigated the association of dietary and lifestyle inflammation scores (DLIS) with the odds of CM in Iranian women. In the current study, 285 women with migraine enrolled. Migraine was diagnosed by a single neurologist based on the third edition of the International Classification of Headache Disorders (ICHD-III). The women were categorized into CM and EM groups based on their attack frequency per month. Adherence to the dietary inflammation score (DIS), Lifestyle Inflammatory Score (LIS), and DLIS (DIS + LIS) was assessed based on last year's dietary intakes collected using a semi-quantitative food frequency questionnaire (FFQ). The Odds Ratio (OR) for CM across the DIS, LIS, and DLIS tertiles were assessed through logistic regression. Most of the participants were overweight or obese (74.4%). The percentage of women with CM was 40.7%. Women with CM had significantly higher DIS (P = 0.002) and DLIS (P = 0.04) than women with EM. There was a significant positive association between CM and DIS. Those in the third tertile of the DIS had almost two times higher chance of experiencing chronic migraine compared with those in the first tertile [OR = 2.02; 95% CI 1.06–3.82; P = 0.03]. the P-value for the trend also was significant (0.03). In terms of LIS and DLIS tertiles, no significant association was observed. Adherence to the more inflammatory diets was associated with higher chances of experiencing CM in women. [ABSTRACT FROM AUTHOR]

Migraine is a complex disorder characterized by episodes of moderate-to-severe, often unilateral headaches and generally accompanied by nausea, vomiting, and increased sensitivity to light (photophobia), sound (phonophobia), and smell (hyperosmia). Photophobia is considered the most bothersome symptom of migraine attacks. Although the underlying mechanism remains unclear, the intrinsically photosensitive retinal ganglion cells (ipRGCs) are considered to be involved in photophobia associated with migraine. In this study, we investigated the association between the sensitivity of ipRGCs and migraines and cortical spreading depression (CSD), which may trigger migraine attacks. The pupillary responses closely associated with the function of ipRGCs in patients with migraine who were irradiated with lights were evaluated. Blue (486 nm) light irradiation elicited a response from ipRGCs; however, red light (560 nm) had no such effect. Melanopsin, a photosensitive protein, phototransduces in ipRGCs following blue light stimulation. Hypersensitivity of ipRGCs was observed in patients with migraine. CSD was more easily induced with blue light than with incandescent light using a mouse CSD model. Moreover, CSD was suppressed, even in the presence of blue light, after injecting opsinamide, a melanopsin inhibitor. The hypersensitivity of ipRGCs in patients with migraine may induce CSD, resulting in migraine attacks. [ABSTRACT FROM AUTHOR]

Even when pain control is implemented, calves may experience pain for days after hot-iron disbudding. Whether calves seek pain relief post-disbudding offers a novel approach to assessing pain in these animals. By employing an approach-aversion paradigm, we explored the ability of cold therapy to provide immediate pain relief in disbudded calves. Calves were habituated to the manual placement of a cool or ambient pack on their forehead for a short duration simultaneous to milk reward consumption, prior to disbudding. Calves were then disbudded under local anaesthesia (procaine) and analgesia (meloxicam), and responses to the packs were observed over subsequent days. Individual calves were consistently exposed to either cool or ambient packs in different halves of a two-sided experimental pen, allowing for the testing of approach-aversion and conditioned place preference. We found calves approached milk rewards quicker and maintained contact for longer when receiving cold therapy compared to the ambient control. However, calves did not display any conditioned preference for the pen where they received the cool pack. These results add to the growing evidence of lasting pain following disbudding procedures and suggests that cold therapy provides some form of pain relief post-disbudding. Future studies should seek other ways to use cold therapy post-disbudding to reduce aversiveness and human involvement. [ABSTRACT FROM AUTHOR]

Medication overuse headache (MOH) is a chronic headache disorder that results from excessive use of acutely symptomatic headache medications, leading to more frequent and severe headaches. This study aims to assess the 3-month treatment outcomes in MOH patients, focusing on the types and usage of overused medications, as well as preventive treatments. This prospective cross-sectional study analyzed the treatment outcomes of 309 MOH patients from April 2020 to March 2022. Patients were advised to discontinue overused medications immediately and offered preventive treatments based on clinical judgment. Data on headache characteristics, medication use, and impact on daily life were collected at baseline and 3 months. Results showed overall significant improvements in headache-related variables in patients completing the 3-month treatment follow-up. The median number of headache days per month decreased from 15 days at baseline to 8 days after 3 months (p < 0.001). Patients who overused multiple drug classes demonstrated increased disability levels (mean Headache Impact Test-6 score: 62 at baseline vs. 56 at 3 months, p < 0.01). Those who continued overusing medications reported more days of severe headache (mean 18 days at baseline vs. 14 days at 3 months, p < 0.05) and greater impact (mean Migraine Disability Assessment score: 35 at baseline vs. 28 after 3 months, p < 0.05) compared to the baseline. Differences in headache outcomes were evident across different preventive treatment groups, with generalized estimating equation analyses highlighting significant associations between clinical characteristics, overused medication classes, and preventive treatments. Most MOH clinical features significantly improved after 3 months of treatment. However, notable interactions were observed with certain clinical presentations, suggesting possible influences of overused medication classes, usage patterns, and preventive treatment types on MOH treatment outcomes. This study underscores the importance of individualized treatment strategies and the potential benefits of discontinuing overused medications. [ABSTRACT FROM AUTHOR]

Objective: Gastroesophageal reflux disease (GERD) and migraine are public health concerns worldwide. No observational study has conclusively elucidated the causal relationship between these two conditions. We employed Mendelian randomization (MR) methods to explore the potential causal links between GERD and migraine. Methods: Genome-wide association studies were subjected to MR to infer the causality between GERD and migraine. Bidirectional two-sample MR was performed to establish causal relationships. Multivariable MR analysis was conducted to adjust potential confounding factors, and mediation MR analysis was utilized to assess the role of depression between GERD and migraine as a mediator. We primarily utilized the inverse variance weighted method (IVW) and sensitivity analysis methods, including MR-Egger, weighted median, and leave-one-out methods. We assessed heterogeneity and pleiotropy to ensure the reliability of the results. Results: Bidirectional two-sample MR revealed a positive causal effect of GERD on migraine (IVW: OR = 1.49, 95% CI: 1.34–1.66, p = 3.70E-13). Migraine did not increase the risk of GERD (IVW: OR = 1.07, 95% CI: 0.98–1.17, p = 0.1139). Multivariable MR indicated that the positive causal effect of GERD on migraine remained after adjustment for factors, such as smoking, alcohol consumption, obesity, type 2 diabetes, and depression. Mediation MR revealed that depression mediated 28.72% of GERD's effect on migraine. MR analysis was supported by all sensitivity analyses and was replicated and validated in another independent dataset on migraine. Conclusion: Our findings elucidate the positive causal effect of GERD on migraine and underscores the mediating role of depression in increasing the risk of migraine due to GERD. Effective control of GERD, particularly interventions targeting depression, may aid in preventing the occurrence of migraine. Future research should delve deeper into the specific pathophysiological mechanisms through which GERD affects migraine risk, facilitating the development of more effective drug targets or disease management strategies. [ABSTRACT FROM AUTHOR]

The clinical phenotype of the so-called late-onset depression (LOD) affecting up to 30% of older adults and yielding heterogeneous manifestations concerning symptoms, severity and course has not been fully elucidated yet. This European, cross-sectional, non-interventional, naturalistic multicenter study systematically investigated socio-demographic and clinical correlates of early-onset depression (EOD) and LOD (age of onset ≥ 50 years) in 1410 adult in- and outpatients of both sexes receiving adequate psychopharmacotherapy. In a total of 1329 patients (94.3%) with known age of disease onset, LOD was identified in 23.2% and was associated with unemployment, an ongoing relationship, single major depressive episodes, lower current suicidal risk and higher occurrence of comorbid hypertension. In contrast, EOD was related to higher rates of comorbid migraine and additional psychotherapy. Although the applied study design does not allow to draw any causal conclusions, the present results reflect broad clinical settings and emphasize easily obtainable features which might be characteristic for EOD and LOD. A thoughtful consideration of age of onset might, hence, contribute to optimized diagnostic and therapeutic processes in terms of the globally intended precision medicine, ideally enabling early and adequate treatment allocations and implementation of respective prevention programs. [ABSTRACT FROM AUTHOR]

Occipital nerve decompression is effective in reducing headache symptoms in select patients with migraine and occipital neuralgia. Eligibility for surgery relies on subjective symptoms and responses to nerve blocks and Onabotulinum toxin A (Botox) injections. No validated objective method exists for detecting occipital headache pathologies. The purpose of the study is to explore the potential of high-resolution Magnetic Resolution Imaging (MRI) in identifying greater occipital nerve (GON) pathologies in chronic headache patients. The MRI protocol included three sequences targeting fat-suppressed fluid-sensitive T2-weighted signals. Visualization of the GON involved generating 2-D image slices with sequential rotation to track the nerve course. Twelve patients underwent pre-surgical MRI assessment. MRI identified four main pathologies that were validated against intra-operative examination: GON entanglement by the occipital artery, increased nerve thickness and hyperintensity suggesting inflammation compared to the non-symptomatic contralateral side, early GON branching with rejoining at a distal point, and a connection between the GON and the lesser occipital nerve. MRI possesses the ability to visualize the GON and identify suspected trigger points associated with headache symptoms. This case series highlights MRI's potential to provide objective evidence of nerve pathology. Further research is warranted to establish MRI as a gold standard for diagnosing extracranial contributors in headaches. [ABSTRACT FROM AUTHOR]

Migraine is a common brain condition characterised by disabling attacks of headache with sensory sensitivities. Despite increasing understanding of migraine neurobiology and the impacts of this on therapeutic developments, there remains a need for treatment options for patients underserved by currently available therapies. The first specific drugs developed to treat migraine acutely, the serotonin-5-hydroxytryptamine [5-HT1B/1D] receptor agonists (triptans), seem to require headache onset in order to have an effect, while early treatment during mild pain before headache escalation improves short-term and long-term outcomes. Some patients find treating in the early window once headache has started but not escalated difficult, and migraine can arise from sleep or in the early hours of the morning, making prompt treatment after pain onset challenging. Triptans may be deemed unsuitable for use in patients with vascular disease and in those of older age and may not be effective in a proportion of patients. Headache is also increasingly recognised as being just one of the many facets of the migraine attack, and for some patients it is not the most disabling symptom. In many patients, painless symptoms can start prior to headache onset and can reliably warn of impending headache. There is, therefore, a need to identify therapeutic targets and agents that may be used as early as possible in the course of the attack, to prevent headache onset before it starts, and to reduce both headache and non-headache related attack burden. Early small studies using domperidone, naratriptan and dihydroergotamine have suggested that this approach could be useful; these studies were methodologically less rigorous than modern day treatment studies, of small sample size, and have not since been replicated. The emergence of novel targeted migraine treatments more recently, specifically calcitonin gene-related peptide (CGRP) receptor antagonists (gepants), has reignited interest in this strategy, with encouraging results. This review summarises historical and emerging data in this area, supporting use of the premonitory phase as an opportunity to intervene as early as possible in migraine to prevent attack-related morbidity. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions We explored whether esketamine anesthesia during hysteroscopic surgery can reduce intraoperative hemodynamic fluctuations and improve patient benefit.A total of 170 patients undergoing hysteroscopic surgery were enrolled, and 151 patients were finally included in the analysis, among which 19 used vasoactive drugs during surgery. Patients were randomly assigned to either the esketamine anesthesia group (E group) or the sufentanil anesthesia group (S group). The primary outcomes were blood pressure and heart rate during the surgery. Secondary outcomes included resistance to laryngeal mask insertion, demand for propofol and remifentanil, nausea and vomiting, Richmond Agitation and Sedation Scale (RASS), dizziness and pain intensity after resuscitation, vasoactive medication treatment, hospitalization time and expenses.E group had a more stable heart rate, systolic blood pressure, diastolic blood pressure and mean blood pressure than the S group (p < 0.001). Patients in E group had a higher demand for propofol (p < 0.001) but better RASS scores (p < 0.001) after resuscitation. The incidence of intraoperative vasoactive medication use was higher in the S group (18.4% vs. 6.7%, p = 0.029). There were no statistically significant differences in terms of resistance to laryngeal mask insertion, remifentanil demand, time required for resuscitation, postoperative pain, dizziness, nausea or vomiting.Compared with sufentanil, esketamine‐induced anesthesia during hysteroscopic surgery can reduce intraoperative hemodynamic fluctuations and the incidence of intraoperative vasoactive medication. Although esketamine‐induced anesthesia may increase the demand for propofol during surgery, it does not affect the anesthesia recovery time and the quality of patient recovery is better. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, several drugs were repositioned and combined to quickly find a way to mitigate the effects of the infection. However, the adverse effects of these combinations on the gastrointestinal tract are unknown. We aimed investigate whether Hydroxychloroquine (HD), Azithromycin (AZ), and Ivermectin (IV) used in combination for the treatment of COVID-19, can lead to the development of gastrointestinal disorders. This is a systematic review and network meta-analysis conducted using Stata and Revman software, respectively. The protocol was registered with PROSPERO (CRD42023372802). A search of clinical trials in Cochrane Library databases, Embase, Web of Science, Lilacs, PubMed, Scopus and Clinicaltrials.gov conducted on November 26, 2023. The eligibility of the studies was assessed based on PICO criteria, including trials that compared different treatments and control group. The analysis of the quality of the evidence was carried out according to the GRADE. Six trials involving 1,686 COVID-19 patients were included. No trials on the association of HD or AZ with IV met the inclusion criteria, only studies on the association between HD and AZ were included. Nausea, vomiting, diarrhea, abdominal pain and increased transaminases were related. The symptoms of vomiting and nausea were evaluated through a network meta-analysis, while the symptom of abdominal pain was evaluated through a meta-analysis. No significant associations with these symptoms were observed for HD, AZ, or their combination, compared to control. Low heterogeneity and absence of inconsistency in indirect and direct comparisons were noted. Limitations included small sample sizes, varied drug dosages, and potential publication bias during the pandemic peak. This review unveils that there are no associations between gastrointestinal adverse effects and the combined treatment of HD with AZ in the management of COVID-19, as compared to either the use of a control group or the administration of the drugs individually, on the other hand, highlighting the very low or low certainty of evidence for the evaluated outcomes. To accurately conclude the absence of side effects, further high-quality randomized studies are needed. [ABSTRACT FROM AUTHOR]

We evaluated associations between diet quality and migraine outcomes. The current work represented a cross-sectional study on 262 patients with migraine (20–50 y). Diet quality was assessed using the standard healthy eating index 2015 (HEI-2015) and alternative healthy eating index 2010 (AHEI-2010). A validated 168-item food frequency questionnaire was used to assess dietary intake. Migraine outcomes included clinical factors (severity, duration, frequency, and disability related to migraine) and serum nitric oxide (NO). Associations between diet quality indices and migraine outcomes were evaluated using linear regressions, and β and 95% corresponding confidence interval (CI) were reported. HEI-2015 was inversely associated with migraine frequency (β = −4.75, 95% CI: −6.73, −2.76) in patients with the highest HEI scores (third tertile) vs. those with the lowest scores (first tertile) after adjusting for relevant confounders. AHEI-2010 was inversely associated with migraine frequency (β = −3.67, 95% CI: −5.65, −1.69) and migraine-related disability (β = −2.74, 95% CI: −4.79, −0.68) in adjusted models. Also, AHEI-2010 was inversely associated with migraine severity in patients in the second vs. first tertile (β = −0.56; 95% CI: −1.08, −0.05). We detected no associations between diet quality and NO levels (All P > 0.14). Improved diet quality may be associated with favorable migraine outcomes (lower headache frequency, severity, and migraine-related disability). Future studies are required to confirm and delineate the causal mechanisms of our observations. [ABSTRACT FROM AUTHOR]

Migraine headaches are the most prevalent disabling primary headaches, affecting individuals at an active age. Dietary interventions are considered low‐cost and practical approaches to migraine prophylaxis. Hence, the present study aimed to assess the association between adherence to the Healthy Eating Index 2015 (HEI‐2015) and migraine headaches. The present case–control study was conducted on 476 newly diagnosed adults with migraine headaches, based on the International Classification of Headache Disorders 3rd edition (ICHDIII criteria(, and 512 healthy controls. Participants' dietary intakes were collected using a validated, 168‐item semi‐quantitative food frequency questionnaire (FFQ). The association between HEI‐2015 and migraine headaches was assessed using logistic regression models. Although the trend was not statistically significant, being in the 4th quantile of the HEI‐2015 was associated with about 50% lower odds of migraine headaches in both primary (adjusted for age and gender) (odds ratios (OR): 0.51, 95% confidence intervals (CI): 0.33, 0.78) and fully adjusted models (additionally adjusted for body mass index (BMI) and total calories) (adjusted OR: 0.50, 95%CI: 0.32, 0.77). Intriguingly, the odds of migraine headaches were significantly higher in those in the last quantile of "Total Fruits," which is equal to more than 237 g per 1000 kcal (aOR: 2.96, 95%CI: 1.99, 4.41) and "Whole Fruits," which is equal to more than 233 g per 1000 kcal (aOR: 2.90, 95%CI: 1.94, 4.31). Similarly, higher intakes of "Dairy," which is equal to more than 138 g per 1000 kcal (aOR: 2.66, 95%CI: 1.71, 4.14), and "Total Protein Foods," which is equal to more than 259 g per 1000 kcal (aOR: 2.41, 95%CI: 1.58, 3.70), were associated with higher odds of migraine headaches. The current study revealed an indirect association between HEI‐2015 and its components, including "Greens and Beans," "Whole Grains," "Refined Grains," and "Added Sugars" and lower odds of migraine headaches. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this real‐life study were to analyze the reversion of chronic migraine (CM) to episodic migraine (EM) with fremanezumab, evaluate its benefit on the symptomatology, and determine the influence of possible clinical features on the reversion. Background: The clinical manifestations of CM have a high impact on the quality of life of patients, and monoclonal antibodies such as fremanezumab are used as prophylactic treatment. Methods: Diagnosed CM patients treated for at least 3 months with monthly fremanezumab were interviewed. The data to assess efficacy were before treatment and at the time of the interview: monthly headache days (MHDs), daily headache hours (DHHs), monthly symptomatic medication days (MSMDs), percentage of patients with symptomatic medication overuse (SMO), and pain intensity with the numerical rating scale (NRS) score. Possible predictors of reversion were analyzed: percentage of patients treated for at least 12 months, hypertension, diabetes mellitus, depression, anxiety, symptomatic control with non‐steroidal anti‐inflammatory drugs (NSAIDs), triptans or both, and amitriptyline prophylaxis. Results: A total of 54 patients were included, of whom 40 (74.1%) were converters to EM. There were significant improvements in converters compared to pre‐treatment in MHDs (28.0 vs. 5.0 days), as well as on the variables DHHs, MSMDs, and SMO. The percentage of erenumab failures was significantly higher in non‐converters than in converters, as was the percentage of patients with anxiety. Conclusions: High reversion from CM to EM was achieved with fremanezumab and notable symptomatological improvement, establishing previous failure to erenumab and anxiety as possible detrimental factors for reversion. [ABSTRACT FROM AUTHOR]

Zavegepant, a high‐affinity, selective, small‐molecule calcitonin gene‐related peptide (CGRP) receptor antagonist, is approved in the United States for acute treatment of migraine in adults. The effects of moderate hepatic impairment (8 participants with Child‐Pugh score 7–9 points) on the pharmacokinetics of a single 10‐mg intranasal dose of zavegepant versus eight matched participants with normal hepatic function were evaluated in a phase I study. Pharmacokinetic sampling determined total and unbound plasma zavegepant concentrations. Moderate hepatic impairment increased the exposure of total zavegepant (~2‐fold increase in AUC0–inf and 16% increase in Cmax) versus normal hepatic function, which is not considered clinically meaningful. The geometric least squares mean ratios (moderate impairment/normal) of plasma zavegepant AUC0−inf and Cmax were 193% (90% confidence interval [CI]: 112, 333; p = 0.051) and 116% (90% CI: 69, 195; p = 0.630), respectively. The geometric mean fraction unbound of zavegepant was similar for participants with moderate hepatic impairment (0.13; coefficient of variation [CV] 13.71%) versus those with normal hepatic function (0.11; CV 21.43%). Similar exposure findings were observed with unbound zavegepant versus normal hepatic function (~2.3‐fold increase in AUC0−inf and 39% increase in Cmax). One treatment‐emergent adverse event (mild, treatment‐related headache) was reported in a participant with normal hepatic function. No dosage adjustment of intranasal zavegepant is required in adults with mild or moderate hepatic impairment. [ABSTRACT FROM AUTHOR]

COVID-19 can cause neurological symptoms such as fever, dizziness, and nausea. However, such neurological symptoms of SARS-CoV-2 infection have been hardly assessed in mouse models. In this study, we infected two commonly used wild-type mouse lines (C57BL/6J and 129/SvEv) and a 129S calcitonin gene-related peptide (αCGRP) null-line with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including fever, dizziness, and nausea. We then evaluated whether a CGRP receptor antagonist, olcegepant, a “gepant” antagonist used in migraine treatment, could mitigate acute neuroinflammatory and neurological signs of SARS-COV-2 infection. First, we determined whether CGRP receptor antagonism provided protection from permanent weight loss in older (>18 m) C57BL/6J and 129/SvEv mice. We also observed acute fever, dizziness, and nausea in all older mice, regardless of treatment. In both wild-type mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels with virtually no IL-6 release in mice lacking αCGRP. These findings suggest that migraine inhibitors such as those blocking CGRP receptor signaling protect against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection, which may have repercussions for related pandemic or endemic coronavirus outbreaks. IMPORTANCE Coronavirus disease (COVID-19) can cause neurological symptoms such as fever, headache, dizziness, and nausea. However, such neurological symptoms of severe acute respiratory syndrome CoV-2 (SARS-CoV-2) infection have been hardly assessed in mouse models. In this study, we first infected two commonly used wild-type mouse lines (C57BL/6J and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological symptoms including fever and nausea. Furthermore, we showed that the migraine treatment drug olcegepant could reduce long-term weight loss and IL-6 release associated with SARS-CoV-2 infection. These findings suggest that a migraine blocker can be protective for at least some acute SARS-CoV-2 infection signs and raise the possibility that it may also impact long-term outcomes. [ABSTRACT FROM AUTHOR]

Interactions of hepatic macrophages with local inflammatory microenvironment is the key factor promoting the development of acute liver failure (ALF). Hence, reprogramming pro-inflammatory M1 into anti-inflammatory M2 phenotype may offer a promising strategy for treating ALF by targeting inflammation. Our group found Carvedilol possessed potential anti-inflammatory property previously, which had been scarcely reported in ALF. We present a synergy strategy to induce macrophages into the phenotype M2-type anti-inflammatory macrophages with interleukin-4 (IL-4) and IL-10 at first. Then Carvedilol is loaded on the macrophage membrane-camouflaged biomimetic nano-platform (termed as M2M@CNP) to evade reticuloendothelial system (RES) and afford Carvedilol delivery to the inflammatory environment with overproduced reactive oxygen species (ROS), further prolonging its circulation and accumulation. Sustainably released Carvedilol produced anti-inflammatory, antioxidant and anti-apoptosis effects, combining local M2-type cell membranes (M2-CM) inhibited pro-inflammatory cytokines and ROS levels, which in turn promoted and amplified M1 to M2 phenotype polarization efficiency. This study offers new insights into the rational design of biomimetic nanosystems for safe and effective ALF therapy to accelerate the clinical translation. [ABSTRACT FROM AUTHOR]

Introduction: In today's fast-paced life, an increasing number of people are experiencing chronic stress, which negatively impacts our mental and physical health, leading to troublesome conditions such as primary headaches. Faced with this challenge, more individuals are turning their attention to mindfulness techniques as an effective tool for stress management. In light of this, mindfulness, focusing on the awareness of the present moment, emerges as a promising method for preventing and alleviating stress-induced headaches and the resulting aftermath. Purpose: Offer a comprehensive overview of the current understanding of the efficacy of mindfulness training, particularly Mindfulness-Based Stress Reduction (MBSR), in the prevention and relief of primary headaches and their associated consequences. Description of the state of knowledge: MBSR demonstrates the potential for effectively coping with stress-induced headaches and their subsequent effects, including disability related to headaches. This category of pain includes conditions like migraine and tension-type headaches. In the clinical trials conducted thus far participants in the MBSR program show noticeable improvement in headache-related disability, self-efficacy, quality of life, catastrophic pain, and depression scores. Summary: Studies suggest that integrating mindfulness training could present a promising strategy for preventing and reducing the severity of primary headaches and their consequences, by mitigating stress, a crucial factor influencing the onset of these headaches. To validate these promising findings, further randomized, large-scale, placebo-controlled studies are required. [ABSTRACT FROM AUTHOR]

Background: Calcitonin gene-related peptide (CGRP), implicated in migraine pain, also possesses bone anabolic properties, which leads to the possibility that monoclonal antibodies targeting CGRP (anti-CGRPs) might increase the risk of bone density abnormalities. Objective: The objective of this study was to explore bone mineral density abnormalities in a cohort of migraine patients treated with anti-CGRPs. Methods: This was a single-center, cross-sectional, cohort study including migraine patients who underwent a densitometry assessment during anti-CGRP treatment. We assessed the frequency of osteopenia or osteoporosis (OSTEO+ status), defined as a bone mineral density T-score of −1 to −2.5, and <−2.5 standard deviations from the young female adult mean, respectively. Additionally, the association of OSTEO+ status with anti-CGRP treatment duration and primary osteoporosis' risk factors was investigated using logistic regression models. Results: Data from 51 patients (43 female, mean age 46 ± 13.9 years) were evaluated. The mean duration of anti-CGRP treatment was 15.7 (±11.8) months. Twenty-seven patients (53%) were OSTEO+ (n = 22 osteopenia; n = 5 osteoporosis). In the final model, menopause [odds ratio 11.641 (95% confidence interval 1.486–91.197), p = 0.019] and anti-seizure drug use [odds ratio 12.825 (95% confidence interval 1.162–141.569), p = 0.037] were associated with OSTEO+ status. Conclusions: In our cohort of migraine patients, no evidence of an association between anti-CGRP treatment duration and an increasing risk of bone mineral density abnormalities was found. However, these findings are preliminary and necessitate further longitudinal research with larger cohorts and extended follow-up to be validated. [ABSTRACT FROM AUTHOR]

Frequent use of pain relief medications among patients with migraine can result in disease worsening and medication-overuse headache (MOH), a painful and debilitating condition. We sought to conduct a cross-sectional survey among adult patients diagnosed with migraine to determine: 1) their awareness of MOH, and 2) their knowledge of the condition and its prevention, and 3) the association of these factors with actual use of pain relief medications. We recruited and interviewed 200 English-speaking adults with migraine who had a clinic visit with a neurologist or primary care provider within the past month. Patients were identified via an electronic health record query. Almost 40% of participants had never heard of the term 'medication-overuse headache.' In bivariate analyses, participants who were Black or Hispanic and those with limited health literacy were less likely to have heard of MOH. Participants scored an average of 2.1 (range: 0–3) on a MOH knowledge measure; older participants, those with limited health literacy, lower education, and little or no migraine-related disability demonstrated less knowledge. Almost a third (31.5%) of patients reported overusing pain relief medication and were at risk for MOH. Overuse was not significantly associated with MOH awareness, knowledge, or sociodemographic factors, but was related to greater migraine-related disability. Our findings suggest that patient awareness and knowledge of MOH is suboptimal, particularly among older adults, racial and ethnic minority groups, and those with limited health literacy. Interventions are needed to prevent MOH and better inform patients about risks associated with frequent use of pain relief medications. [ABSTRACT FROM AUTHOR]

Objective: To assess the potential of ferroptosis and ferritinophagy in migraine pathogenesis. Background: Ferroptosis and ferritinophagy are related to increased cellular iron concentration and have been associated with the pathogenesis of several neurological disorders, but their potential in migraine pathogenesis has not been explored. Increased iron deposits in some deep brain areas, mainly periaqueductal gray (PAG), are reported in migraine and they have been associated with the disease severity and chronification as well as poor response to antimigraine drugs. Results: Iron deposits may interfere with antinociceptive signaling in the neuronal network in the brain areas affected by migraine, but their mechanistic role is unclear. Independently of the location, increased iron concentration may be related to ferroptosis and ferritinophagy in the cell. Therefore, both phenomena may be related to increased iron deposits in migraine. It is unclear whether these deposits are the reason, consequence, or just a correlate of migraine. Still, due to migraine-related elevated levels of iron, which is a prerequisite of ferroptosis and ferritinophagy, the potential of both phenomena in migraine should be explored. If the iron deposits matter in migraine pathogenesis, they should be mechanically linked with the clinical picture of the disease. As iron is an exogenous essential trace element, it is provided to the human body solely with diet or supplements. Therefore, exploring the role of iron in migraine pathogenesis may help to determine the potential role of ironrich/poor dietary products as migraine triggers or relievers. Conclusion: Ferroptosis and ferritinophagy may be related to migraine pathogenesis through iron deposits in the deep areas of the brain. [ABSTRACT FROM AUTHOR]

Background: Sepsis-associated acute kidney injury (SA-AKI) poses an independent risk for mortality due to the absence of highly sensitive biomarkers and a specific treatment plan. Objective: Investigate the association between low molecular weight heparin (LMWH) calcium therapy and prognosis in critically ill SA-AKI patients, and assess the causal relationship through Mendelian randomization (MR) analysis. Methods: A single-center, retrospective, cross-sectional study included 90 SAAKI patients and 30 septic patients without acute kidney injury (AKI) from the intensive care unit (ICU) of the First Hospital of Lanzhou University. SA-AKI patients were categorized into control or LMWH groups based on LMWH calcium usage. Primary outcome was renal function recovery, with secondary outcomes including 28-day mortality, ICU stay length, number of renal replacement therapy (RRT) recipients, and 90-day survival. MR and related sensitivity analyses explored causal effects. Results: The combination of heparin-binding protein (HBP), heparanase (HPA), and neutrophil gelatinase-associated lipocalin (NGAL) demonstrated high diagnostic value for SA-AKI. MR analysis suggested a potential causal link between gene-predicted HBP and AKI (OR: 1.369, 95%CI: 1.040-1.801, p = 0.024). In the retrospective study, LMWH-treated patients exhibited improved renal function, reduced levels of HPA, HBP, Syndecan-1, and inflammation, along with enhanced immune function compared to controls. However, LMWH did not impact 28-day mortality, 90-day survival, or ICU stay length. Conclusion: LMWH could enhance renal function in SA-AKI patients. MR analysis supports this causal link, underscoring the need for further validation in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background and purpose: The efficacy of intravenous thrombolysis (IVT) in patients with acute minor ischaemic stroke (AMIS) remains unclear. We performed a meta-analysis to compare the efficacy and safety of IVT and dual antiplatelet therapy (DAPT) in patients with AMIS. Methods: The Embase, Cochrane Library, PubMed, and Web of Science databases were searched up to 10 October, 2023. Prospective and retrospective studies comparing the clinical outcomes of IVT and DAPT were included. Odds ratios (ORs) and 95% confidence intervals (CIs) for early neurological deterioration (END), excellent and favourable functional outcomes, recurrent ischaemic stroke at 3months, mortality at 3 months, and symptomatic intracranial haemorrhage (ICH) were pooled using a random-effects model. Results: Of the five included studies, 6,340 patients were included. In patients with AMIS, IVT was not significantly associated with excellent and favourable functional outcomes, recurrent ischaemic stroke, or all-cause mortality at 3 months compared to early DAPT. However, a higher risk of symptomatic ICH (OR, 9.31; 95% CI, 3.39-25.57) and END (OR, 2.75; 95% CI, 1.76-4.30) were observed with IVT. Conclusion: This meta-analysis indicated that IVT was not superior to DAPT in patients with AMIS, especially in those with nondisabling AIS. However, these findings should be interpreted with caution and have some limitations. Further, well-designed randomised controlled trials are warranted. [ABSTRACT FROM AUTHOR]

This study aims to investigate auditory hypersensitivity and cortical function in migraine patients using the Hyperacusis Questionnaire and the Event-Related Potential (ERP) technique. The study analyzes alterations in the latency and amplitude of the event-related potentials MMN and P300 components. The findings contribute to a better understanding of the physiological relationship between migraine and auditory hypersensitivity. Seventeen migraine patients were admitted to the outpatient clinic of the Department of Otorhinolaryngology-Head and Neck Surgery at Peking University People's Hospital from June 2023 to September 2023. Nineteen matched healthy subjects were also selected. All participants underwent the pure tone audiometry and the auditory brainstem response test to determine hearing thresholds, the Hyperacusis Questionnaire, the Tinnitus Handicap Inventory, and an ERP examination. The Oddball classical paradigm was used as the stimulation task, and electroencephalography signals were recorded synchronously. The scores of the Hyperacusis Questionnaire, latency and amplitude of MMN and P300 component were compared between the migraine group and the control group, and their correlation was analyzed. The latency of MMN at the Fz and Cz sites in migraine patients was significantly shorter than that in the control group (P < 0.05), and the amplitudes were significantly higher than those in the control group (P < 0.05). The variances in latency and amplitude of P300 at Cz and Pz sites in migraine patients were not statistically significant when compared with the control group. (P > 0.05). The Hyperacusis Questionnaire was negatively correlated with MMN latency, with a correlation coefficient of − 0.374 (P = 0.025), and positively correlated with MMN amplitude, with a correlation coefficient of 0.378 (P = 0.023). There was no significant similarity between the Hyperacusis Questionnaire and P300 latency and amplitude (P > 0.05). Overall, auditory hypersensitivity was enhanced in individuals with migraines compared to healthy individuals, leading to faster information processing, while there may be less impairment in cognitive function. [ABSTRACT FROM AUTHOR]

Optimal strategy for volume control and the clinical implication of achieved volume control are unknown in patients with sepsis-associated acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). This randomized controlled trial aimed to compare the survival according to conventional or bioelectrical impedance analysis (BIA)-guided volume control strategy in patients with sepsis-associated AKI receiving CRRT. We also compared patient survival according to achieved volume accumulation rate ([cumulative fluid balance during 3 days × 100]/fluid overload measured by BIA at enrollment) as a post-hoc analysis. We randomly assigned patients to conventional volume control strategy (n = 39) or to BIA-guided volume control strategy (n = 34). There were no differences in 28-day mortality (HR, 1.19; 95% CI, 0.63–2.23) or 90-day mortality (HR, 0.99; 95% CI 0.57–1.75) between conventional and BIA-guided volume control group. In the secondary analysis, achieved volume accumulation rate was significantly associated with patient survival. Compared with the achieved volume accumulation rate of ≤ − 50%, the HRs (95% CIs) for the risk of 90-day mortality were 1.21 (0.29–5.01), 0.55 (0.12–2.48), and 7.18 (1.58–32.51) in that of − 50–0%, 1–50%, and > 50%, respectively. Hence, BIA-guided volume control in patients with sepsis-associated AKI receiving CRRT did not improve patient outcomes. In the secondary analysis, achieved volume accumulation rate was associated with patient survival. [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcome (PRO) is a distinct and indispensable dimension of clinical characteristics and recent advances have made remote PRO measurement possible. Sex difference in PRO of Parkinson's disease (PD) is hardly extensively researched. Methods: A smartphone-based self-management platform, offering remote PRO measurement for PD patients, has been developed. A total of 1828 PD patients, including 1001 male patients and 827 female patients, were enrolled and completed their PRO submission through this platform. Results: Sex differences in PROs have been identified. The female group had a significantly lower height, weight, and body mass index (BMI) than the male group (P < 0.001). For motor symptoms, a higher proportion of patients reporting dyskinesia was observed in the female group. For non-motor symptoms, there is a higher percentage (P < 0.001) as well as severity (P = 0.016) of depression in the female group. More male patients reported hyposmia, lisp, drooling, dysuria, frequent urination, hypersexuality, impotence, daytime sleepiness, and apathy than females (P < 0.05). In contrast, more female patients reported headache, palpation, body pain, anorexia, nausea, urinal incontinence, anxiety, insomnia (P < 0.05) than males. Conclusions: We provide evidence for sex differences in PD through the data collected from our platform. These results highlighted the importance of gender in clinical decision-making, and also support the feasibility of remote PRO measurement through a smartphone-based self-management platform in patients with PD. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess the knowledge and perceptions of the public toward migraine in Saudi Arabia. Methods: This cross-sectional survey assessed the knowledge and perceptions of migraine among Saudi Arabian individuals. The study was conducted over three months in 2023 (1st of June 2023 to 31st of August 2023) using a prevalidated online questionnaire divided into four sections. Results: A total of 1,975 adults aged between 18 and 64 completed the web-based survey. Of these, over half were male (n = 1,268; 64.2%). The main causes of migraine identified by the participants were genetic disease (n = 540, 27.3%), followed by physical disease (n = 341, 17.3%), head trauma (n = 274, 13.9%), and psychiatric disease (n = 157, 7.9%). The main symptoms identified by the participants were photophobia (21%), followed by inability to control urine (14.1%), vomiting and nausea (13.8%), and vision loss (8.3%). The majority of the participants in this study had a good knowledge of migraines, while 49% had poor knowledge. The migraine knowledge score was significantly associated with the participants' gender (p = 0.002), age (p = 0.0001), educational level (p = 0.001), employment status (p = 0.001), monthly income (p = 0.0001), region (p = 0.0001), and history of migraine (p = 0.0001). Conclusion: Although one-third of the participants exhibiting good knowledge, deficiencies existed in certain clinical aspects, emphasizing the need for targeted educational interventions to enhance public awareness and understanding of migraines. [ABSTRACT FROM AUTHOR]