Long-term persistence to OnabotulinumtoxinA to prevent chronic migraine: Results from 11 years of patient data from a tertiary headache center.

OBJECTIVE: To determine if patients with chronic migraine continue onabotulinumtoxinA (onabotA) long-term. METHODS: We performed a retrospective cohort analysis using aggregated, de-identified patient data from the Stanford Headache Center. We included patients in California who received at least one prescription for onabotA during the years of 2011-2021. The primary outcome was the number of onabotA treatments each patient received. Secondary outcomes included sex, age, race, ethnicity, body mass index (BMI), distance to the treatment facility, and zip code income quartile. RESULTS: A total of 1,551 patients received a mean of 7.60 ± 7.26 treatments and a median of 5 treatments, with 16.2% of patients receiving only one treatment and 10.6% receiving at least 19. Time-to-event survival analysis suggested 26.0% of patients would complete at least 29 treatments if able. Younger age and female sex were associated with statistically significant differences between quartile groups of number of onabotA treatments (p = 0.007, p = 0.015). BMI, distance to treatment facility, and zip code income quartile were not statistically significantly different between quartile groups (p > 0.500 for all). Prescriptions of both triptans and non-onabotA preventive medications showed a statistically significant increase with each higher quartile of number of onabotA treatments (p < 0.001; p < 0.001). DISCUSSION: We show long-term persistence to onabotA is high and that distance to treatment facility and income are not factors in continuation. Our work also demonstrates that as patients continue onabotA over time, there may be an increased need for adjunctive or alternative treatments.

Alcohol Use Disorder in Patients with Chronic Migraine: A Retrospective, Observational Study.

OBJECTIVE: The relationship between migraine and alcohol consumption is unclear. We assessed the association between chronic migraine and alcohol use disorder(AUD), relative to chronic disease controls, and in conjunction with common comorbidities. METHODS: We conducted a retrospective, observational study. The primary outcome was the odds ratio for AUD in patients with chronic migraine or with chronic migraine and additional comorbidities relative to controls. RESULTS: A total of 3701 patients with chronic migraine, 4450 patients with low back pain, and 1780 patients with type 2 diabetes mellitus met inclusion criteria. Patients with chronic migraine had a lower risk of AUD relative to both controls of low back pain (OR 0.37; 95% CI: 0.29-0.47, p < 0.001) and type 2 diabetes mellitus (OR 0.39; 95% CI: 0.29-0.52, p < 0.001). Depression was associated with the largest OR for AUD in chronic migraine (OR 8.62; 95% CI: 4.99-14.88, p < 0.001), followed by post-traumatic stress disorder (OR 6.63; 95% CI: 4.13-10.64, p < 0.001) and anxiety (OR 3.58; 95% CI: 2.23-5.75, p < 0.001). CONCLUSION: Patients with chronic migraine had a lower odds ratio of AUD relative to controls. But in patients with chronic migraine, those with comorbid depression, anxiety, or PTSD are at higher risk of AUD. When patients establish care, comorbid factors should be assessed and for those at higher risk, AUD should be screened for at every visit.

The introduction of the CGRP monoclonal antibodies and their effect on the prescription patterns of chronic migraine preventive medications in a tertiary headache center: A retrospective, observational analysis.

OBJECTIVE: To determine the effect of the introduction of the calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) in 2018 on the prescribing of older medications for the prevention of chronic migraine. BACKGROUND: Prior to 2018, the preventive treatment of migraine borrowed from medications intended to treat other illnesses with the last medication, onabotulinumtoxinA, receiving Food and Drug Administration (FDA) approval for the prevention of chronic migraine in 2010. The FDA approval of three CGRP mAbs in 2018 provided the ideal natural experiment to assess how the introduction of these medications, and a fourth in 2020, affected the generally stable migraine preventive medications market. METHODS: We performed a retrospective cohort analysis using the aggregated de-identified data of 6595 patients. The percentage of patients with chronic migraine who had been prescribed one of ten most prescribed oral preventive medications or onabotulinumtoxinA, or any of the four CGRP mAbs, were calculated relative to the total number of patients with chronic migraine who received a prescription for any medication from our clinic during the pre-CGRP mAb years of 2015-2017 and post-approval years of 2019-2021. RESULTS: We observed a statistically significant decrease in the prescription of the top 10 most prescribed medications after the introduction of the CGRP mAbs overall (1456/3144, 46.3%, to 1995/4629, 43.1%, p = 0.001), as well as with most individual medications, including large decreases in verapamil (230/3144, 7.3%, to 125/4629, 2.7%; p < 0.001), the tricyclic antidepressants (494/3144, 15.7%, to 532/4629, 11.5%; p < 0.001), topiramate (566/3144, 18.0%, to 653/4629, 14.1%; p < 0.001), and onabotulinumtoxinA (861/3144, 27.4%, to 1134/4629, 24.5%; p = 0.001). CONCLUSION: The introduction of the CGRP mAbs during 2018 resulted in a decrease in utilization of most oral medications and onabotulinumtoxinA for the prevention of migraine. Future work should continue to observe how the prescription patterns of these medications evolve with time.

The utility of ChatGPT in the assessment of literature on the prevention of migraine: an observational, qualitative study.

Background: It is not known how large language models, such as ChatGPT, can be applied toward the assessment of the efficacy of medications, including in the prevention of migraine, and how it might support those claims with existing medical evidence. Methods: We queried ChatGPT-3.5 on the efficacy of 47 medications for the prevention of migraine and then asked it to give citations in support of its assessment. ChatGPT's evaluations were then compared to their FDA approval status for this indication as well as the American Academy of Neurology 2012 evidence-based guidelines for the prevention of migraine. The citations ChatGPT generated for these evaluations were then assessed to see if they were real papers and if they were relevant to the query. Results: ChatGPT affirmed that the 14 medications that have either received FDA approval for prevention of migraine or AAN Grade A/B evidence were effective for migraine. Its assessments of the other 33 medications were unreliable including suggesting possible efficacy for four medications that have never been used for the prevention of migraine. Critically, only 33/115 (29%) of the papers ChatGPT cited were real, while 76/115 (66%) were "hallucinated" not real papers and 6/115 (5%) shared the names of real papers but had not real citations. Conclusion: While ChatGPT produced tailored answers on the efficacy of the queried medications, the results were unreliable and inaccurate because of the overwhelming volume of "hallucinated" articles it generated and cited.

The Role of Step Therapy in the Treatment of Migraine.

PURPOSE OF REVIEW: This review examines recent evidence and applies bioethical principles to evaluate the benefits and risks of using step therapy in the treatment of migraine. RECENT FINDINGS: With the CGRP mAbs, gepants, and lasmiditan now on the market for up to 5 years, new research, including network meta-analyses and long-term use studies, can evaluate the comparative efficacy, tolerability, and adherence of these medications relative to older acute and preventive medications for the treatment of migraine. Deciding how medications are chosen for patients requires accounting for many factors including sustainability, efficacy, tolerability, and preference. Newer research can help give clarity on the appropriateness of gating certain treatment options behind others.

The impact of COVID-19 on alcohol sales and consumption in the United States: A retrospective, observational analysis.

Understanding the COVID-19 pandemic's effect on alcohol sales and consumption is critical in mitigating alcohol abuse and morbidity. We sought to determine how the onset of the COVID-19 pandemic and changes in viral incidence affected alcohol sales and consumption in the United States. We conducted a retrospective observational analysis regressing National Institute on Alcohol Abuse and Alcoholism (NIAAA) alcohol sales data and Behavioral Risk Factor Surveillance System (BRFSS) survey data for 14 states for 2017 to 2020 with COVID-19 incidence in 2020 in the United States. The onset of the pandemic was associated with higher monthly alcohol sales per capita of 1.99 standard drinks (95% Confidence Interval: 0.63 to 3.34, p = 0.007). Increases of one COVID-19 case per 100 were associated with lower monthly alcohol sales per capita of 2.98 standard drinks (95% CI: -4.47 to -1.48, p = 0.001) as well as broad decreases in alcohol consumption, notably 0.17 fewer days per month with alcohol use (95% CI: -0.31 to -0.23, p = 0.008) and 0.14 fewer days per month of binge drinking (95% CI: -0.23 to -0.052, p < 0.001). The COVID-19 pandemic is associated with increased monthly average alcohol purchases, but higher viral incidence is linked to lower alcohol purchases and consumption. Continued monitoring is needed to mitigate the effects of higher population alcohol use during the pandemic.

Headache and Dizziness after Roller Coaster Rides: A Case Series of 31 Patients.

Previous literature on roller coaster injuries focuses on catastrophic injuries. We conducted a retrospective study of 31 adults with headache or dizziness after roller coaster rides. Twenty five of 31 (81%) patients presented with new or worsening headache, predominantly migraine (15/25, 60%), including 8/25 (32%) with chronic migraine. Of the chronic migraine patients, 4/8 (50%) already had the diagnosis and presented with an exacerbation. Five of the 25 (20%) were ultimately found to have a cerebrospinal fluid (CSF) leak. While persistent symptoms appear to be relatively rare, patients with chronic migraine and potential CSF leaks should consider skipping these attractions.

Protracted headache after COVID-19: A case series of 31 patients from a tertiary headache center.

BACKGROUND: Headache can be a prominent feature of Post-Acute Sequelae of SARS-Cov2 infection (PASC) and previous studies have centered around PASC headaches that have resolved within a month of infection. METHODS: We performed a retrospective chart review of 31 adults evaluated at the Stanford Headache Clinic between September 2020 and January 2022 who developed new or worsening headaches after COVID-19 infection that were unresolved at time of evaluation for demographics, medical history, and headache diagnosis. RESULTS: Headache had been present for a mean duration of 7.4±4.8 months after infection. Notably, 25/31 (81%) had a previous history of headache. The specific features of the headache varied considerably, but 23/31 (74%) met International Classification of Headache Disorders, Third Edition (ICHD-3) criteria for migraine, with 20/31 (65%) meeting ICHD-3 criteria for chronic migraine, while only 5/31 (16%) met these criteria before COVID infection. Additionally, full-time employment decreased from 25/31 (81%) to 17/31 (55%). Prior to establishing care at our clinic, 13/18 (72%) of the patients who were started on preventive medications currently indicated for migraine management, reported a decrease in frequency and/or severity of headaches. CONCLUSIONS: Our study presents a group of patients with protracted headache after COVID-19 infection that includes both patients with a previously lower headache burden who largely exhibited chronification from episodic to chronic migraine, as well as patients with no previous history of headache who meet ICHD-3 criteria for headache attributed to a systemic viral illness, mostly with a migrainous phenotype.

Migraine and Diet: Updates in Understanding.

PURPOSE OF REVIEW: We explore recent developments in the prevention and treatment of migraine through dietary interventions. RECENT FINDINGS: Healthier diets (defined in multiple ways), meal regularity, and weight loss are associated with decreased headache burden. Specific diets including the ketogenic diet, the low-glycemic index diet, and the DASH diet are supported by modest evidence for the prevention of migraine. Neither a gluten-free diet, in patients without celiac disease, nor elimination diets have sufficient evidence for their routine consideration. Diet remains a crucial, but underexplored, component of comprehensive migraine management. Multiple interventions exist for providers and patients to consider integrating into their treatment plan. Larger studies are needed to support stronger recommendations for utilization of specific dietary interventions for the prevention and treatment of migraine.

Staphylococcus intermedius Brain Abscess as a Complication of Pulmonary Arteriovenous Malformation in a Patient With Hereditary Hemorrhagic Telangiectasia.

Staphylococcus intermedius is a rare cause of human infections ranging from skin and soft tissue infections to bacteremia. It is particularly known for its association with exposure to dogs. We report an unusual case of a 73-year-old female with a brain abscess caused by S intermedius who was recently diagnosed with hereditary hemorrhagic telangiectasia and a pulmonary arteriovenous malformation. The patient underwent debridement of the brain abscess followed by a 6-week course of vancomycin and rifampin, after which she made a near complete recovery. This is the first case of a brain abscess in an adult due to S intermedius in the published literature, and we provide a comprehensive review of the literature of all human infections caused by this pathogen and summarize its clinical manifestations, treatment recommendations, and outcomes.

PhdA Catalyzes the First Step of Phenazine-1-Carboxylic Acid Degradation in Mycobacterium fortuitum.

Phenazines are a class of bacterially produced redox-active metabolites that are found in natural, industrial, and clinical environments. In Pseudomonas spp., phenazine-1-carboxylic acid (PCA)-the precursor of all phenazine metabolites-facilitates nutrient acquisition, biofilm formation, and competition with other organisms. While the removal of phenazines negatively impacts these activities, little is known about the genes or enzymes responsible for phenazine degradation by other organisms. Here, we report that the first step of PCA degradation by Mycobacterium fortuitum is catalyzed by a phenazine-degrading decarboxylase (PhdA). PhdA is related to members of the UbiD protein family that rely on a prenylated flavin mononucleotide cofactor for activity. The gene for PhdB, the enzyme responsible for cofactor synthesis, is present in a putative operon with the gene encoding PhdA in a region of the M. fortuitum genome that is essential for PCA degradation. PhdA and PhdB are present in all known PCA-degrading organisms from the ActinobacteriaM. fortuitum can also catabolize other Pseudomonas-derived phenazines such as phenazine-1-carboxamide, 1-hydroxyphenazine, and pyocyanin. On the basis of our previous work and the current characterization of PhdA, we propose that degradation converges on a common intermediate: dihydroxyphenazine. An understanding of the genes responsible for degradation will enable targeted studies of phenazine degraders in diverse environments.IMPORTANCE Bacteria from phylogenetically diverse groups secrete redox-active metabolites that provide a fitness advantage for their producers. For example, phenazines from Pseudomonas spp. benefit the producers by facilitating anoxic survival and biofilm formation and additionally inhibit competitors by serving as antimicrobials. Phenazine-producing pseudomonads act as biocontrol agents by leveraging these antibiotic properties to inhibit plant pests. Despite this importance, the fate of phenazines in the environment is poorly understood. Here, we characterize an enzyme from Mycobacterium fortuitum that catalyzes the first step of phenazine-1-carboxylic acid degradation. Knowledge of the genetic basis of phenazine degradation will facilitate the identification of environments where this activity influences the microbial community structure.