Diversity, Equity, and Inclusion in Headache Care and Research.

ABSTRACT: This article reviews the disparities faced by individuals who experience headache disorders and discusses potential solutions to deliver equitable care. Disparities exist in the diagnosis and treatment of headache disorders with regard to race, ethnicity, sex, gender, sexual orientation, geography, and socioeconomic status. Furthermore, research in the realm of headache disparities is inadequate, and the clinical trial representation of patients from underserved communities is poor. Many barriers exist to optimizing care for underserved communities and this article addresses these barriers and presents ways to combat them.

Comparative efficacy, quality of life, safety, and tolerability of atogepant and rimegepant in migraine prevention: A matching-adjusted indirect comparison analysis.

BACKGROUND: Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. METHODS: An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1-12. RESULTS: There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1-12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: -1.65 [-2.49, -0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. CONCLUSION: In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.

Temporal analysis of remote electric neuromodulation for the prevention of migraine.

Aim: To evaluate the onset, magnitude and persistence of efficacy of remote electrical neuromodulation (REN) compared with placebo for the preventive treatment of migraine. Materials & methods: Analysis was conducted on data from a prospective, double-blind, placebo-controlled clinical trial, which assessed the efficacy of REN for the prevention of migraine. The number of monthly migraine days (MMD) per group was calculated in 2-week intervals and compared between the groups. Results: Differences between the active (N = 95) and placebo (N = 84) groups reached significance at 2 weeks: therapeutic gain 0.84 MMD; p = 0.036. 4 weeks gain 1.59 MMD; p = 0.025, 6 weeks gain 2.27 MMD; p < 0.001, 8 weeks gain 2.68 MMD; p < 0.001. Conclusion: REN provides rapid and consistent efficacy in preventive treatment of migraine.

Patient-reported migraine-specific quality of life, activity impairment and headache impact with once-daily atogepant for preventive treatment of migraine in a randomized, 52-week trial.

BACKGROUND: Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist for the preventive treatment of episodic migraine. METHODS: In this 52-week, multicenter, randomized, open-label trial, adults with 4-14 monthly migraine days received atogepant 60 mg once-daily or standard care. Health outcome endpoints collected from participants randomized to atogepant included change from baseline in Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1) Role Function-Restrictive (RFR), Role Function-Preventive (RFP) and Emotional Function (EF) domain scores, change in Activity Impairment in Migraine-Diary (AIM-D) Performance of Daily Activities (PDA) and Physical Impairment (PI) domain scores, and change in Headache Impact Test-6 (HIT-6) total score. RESULTS: Of 744 randomized participants, 521 received atogepant 60 mg in the modified intent-to-treat population. Least-squares mean changes from baseline in MSQ-RFR score were 30.02 (95% confidence interval = 28.16-31.87) at week 12 and 34.70 (95% confidence interval = 32.74-36.66) at week 52. Improvements were also observed in other MSQ domains, AIM-D PDA, PI and HIT-6 total scores. A ≥5-point improvement from baseline in HIT-6 score was observed in 59.9% of participants at week 4 and 80.8% of participants at week 52. CONCLUSION: Over 52 weeks, atogepant 60 mg once-daily was associated with sustained improvements in quality of life and reductions in activity impairment and headache impact.Trial Registration: NCT03700320.

Harassment in the headache field: a global web-based cross-sectional survey.

BACKGROUND: Matters of workplace harassment are an important issue. This issue needs to be recognized and studied to prevent occurrences. These important sensitive areas of effective workplace management are increasingly gaining more interest. We aimed to identify the prevalence of workplace sexual, verbal and physical harassment among headache professionals. METHODS: We adopted a cross­sectional exploratory survey approach with quantitative design. The survey was distributed electronically among headache healthcare and research professionals globally through the International Headache Society (IHS). RESULTS: Data were obtained from 579 respondents (55.3%; 320/579 women). A large percentage of respondents (46.6%; 270/579) had experienced harassment; specifically, 16.1% (93/578) reported sexual harassment, 40.4% (234/579) verbal harassment and 5.5% (32/579) physical harassment. Women were almost seven times more likely to experience sexual harassment compared to men (odds ratio = 6.8; 95% confidence interval = 3.5-13.2). Although women did also more frequently report other types of harassment, this was not statistically significant (odds ratio = 1.4; 95% confidence interval = 1.0-2.0). CONCLUSIONS: Lifetime exposure to workplace harassment is prevalent among headache professionals, especially in women. The present study uncovers a widespread issue and calls for strategies to be implemented for building a healthy and safe workplace environment.

A qualitative evidence synthesis of patient perspectives on migraine treatment features and outcomes.

OBJECTIVES: We aimed to identify migraine treatment features preferred by patients and treatment outcomes most valued by patients. BACKGROUND: The values and preferences of people living with migraine are critical for both the choice of acute therapy and management approach of migraine. METHODS: We conducted a qualitative evidence synthesis. Two reviewers independently selected studies, appraised methodological quality, and undertook a framework synthesis. We developed summary of findings tables following the approach of Grading of Recommendations, Assessment, Development and Evaluations Confidence in the Evidence from Reviews of Qualitative Research to assess confidence in the findings. RESULTS: Of 1691 candidate references, we included 19 studies (21 publications) involving 459 patients. The studies mostly recruited White women from North America (11 studies) and Europe (8 studies). We identified eight themes encompassing features preferred by patients in a migraine treatment process. Themes described a treatment process that included shared decision-making, a tailored approach, trust in health-care professionals, sharing of knowledge and diversity of treatment options, a holistic approach that does not just address the headache, ease of communication especially for complex treatments, a non-undermining approach, and reciprocity with mutual respect between patient and provider. In terms of the treatment itself, seven themes emerged including patients' preferences for nonpharmacologic treatment, high effectiveness, rapidity of action, long-lasting effect, lower cost and more accessibility, self-management/self-delivery option that increases autonomy, and a mixed preference for abortive versus prophylactic treatments. The treatment outcomes that have high value to patients included maintaining or improving function; avoiding side effects, potential for addiction to medications, and pain reoccurrence; and avoiding non-headache symptoms such as nausea, vomiting, and sensitivity to light or sounds. CONCLUSION: Patient values and preferences were individually constructed, varied widely, and could be at odds with conventional medical perspectives and evidence of treatment effects. Considering the availability of numerous treatments for acute migraine, it is necessary that decision-making incorporates patient values and preferences identified in qualitative research. The findings of this qualitative synthesis can be used to facilitate an individually tailored approach, strengthen the patient-health-care system relationship, and guide choices and decisions in the context of a clinical encounter or a clinical practice guideline.

Post hoc analysis of clinical trial data and pharmacokinetic data to assess wearing-off of erenumab within monthly treatment cycle.

BACKGROUND: Treatment wearing-off has been reported for calcitonin gene-related peptide-pathway monoclonal antibodies, including erenumab, specifically in the last week of the monthly dosing cycle. OBJECTIVE: We sought to determine the consistency of erenumab effect throughout the monthly treatment cycle. METHODS: In this post hoc analysis of four pivotal double-blind, randomized controlled studies of erenumab in episodic and chronic migraine, we assessed wearing-off based on change in weekly migraine days at week 4 versus average over weeks 1-3 in each monthly dosing cycle. Analyses were conducted at each monthly dosing cycle in all patients, in responders (≥50% reduction in weekly migraine days), and in consistent responders (response in ≥2monthly cycles). RESULTS: There was no evidence of wearing-off in the full study populations of two global studies (N = 946 and N = 656) and two Japan studies (N = 475 and N = 261). In the full study population, mean change in weekly migraine days at week 4 compared with the average over week 1-3 ranged from 0.15 days improvement to 0.19 days worsening in the placebo group and 0.08 days improvement to 0.20 days worsening in the erenumab groups. A subgroup of responders experienced wearing-off, but the extent of wearing-off did not differ between erenumab and placebo groups. The mean change in weekly migraine days at week 4 compared with the average over weeks 1-3 ranged from 0.34 to 0.61 days worsening in the placebo group and 0.27 to 0.78 days worsening in the erenumab groups. Few patients had persistent wearing-off in ≥2 consecutive monthly treatment cycles. For erenumab-treated responders, serum erenumab concentrations were similar among patients experiencing wearing-off and those maintaining response. CONCLUSION: No systematic wearing-off with erenumab was identified. Further research is needed to determine if wearing-off reported for some patients in clinical practice reflects a true treatment response pattern or normal fluctuations in migraine frequency.

Incidence of Status Migrainosus in Olmsted County, Minnesota, United States: Characterization and Predictors of Recurrence.

BACKGROUND AND OBJECTIVES: SM is recognized as a complication of migraine in which pain and/or associated symptoms are unremitting and debilitating for more than 72 hours. The epidemiology of SM in the general population is not known. The aim of this study is to determine the incidence, recurrence rate, and clinical associations of status migrainosus (SM) in care-seeking residents of Olmsted County, Minnesota. METHODS: The Rochester Epidemiology Project was used to identify the incident cases of SM according to the International Classification of Headache Disorders, Third Edition criteria and based on the first physician-encountered case in the record. The clinical characteristics of the incident cases were abstracted from the medical record. One-year recurrence-free survival was evaluated and compared between clinically relevant groups, including baseline demographics, migraine characteristics, and treatment exposures. RESULTS: Between January 1, 2012, and December 31, 2017, 237 incident cases of SM were identified. The median age was 35 (IQR 26-47) years, and 210 (88.6%) were female. A history of chronic migraine was recorded in 82/226 (36.3%) and a history of aura in 76/213 (35.7%). At the time of the incident case, medication reconciliation included a triptan or ergotamine in 127/233 (53.6%) and/or an opioid-containing analgesic in 43/233 (18.5%). The overall age- and sex-adjusted incidence rate was 26.60 per 100,000 [95% CI, 23.21-29.97], with a peak incidence between ages 40 and 49 years. The median (95% CI) attack duration was 5 (4.48-5.42) days. The most frequent triggers were stress (40/237, 16.9%) and too much or too little sleep (27/237, 11.4%). Recurrence occurred in 35/237 (14.8%) at a median of 58 (IQR 23-130) days following the initial attack. In our age- and sex-adjusted multivariable model, too much or too little sleep as a trigger was associated with 12-month risk of recurrence (adjusted OR 3.59 [95% CI 1.58-8.14], p = 0.0022). DISCUSSION: Our study provides a population-based estimate of SM incidence. We identified aberrant sleep patterns as a potentially modifiable risk factor for 1-year SM recurrence.

Acute Treatment of Headache (Focus on Migraine).

Acute treatments for migraine and cluster headache are necessary to abort attacks, relieve pain and associated symptoms, and restore an individual's ability to function. Acute headache treatments consist of a variety of medication and nonmedication options. In this article, we discuss the approach to acute treatment of migraine and cluster headache. We summarize the level of evidence to support each acute medication class according to recent systematic reviews and meta-analyses, as well as guideline recommendations from the American Headache Society, American Academy of Neurology, and European Federation of Neurological Society.

Perceived barriers to career progression in the headache field: A global web-based cross-sectional survey.

BACKGROUND: It is well recognized that underrepresented and minoritized groups do not have the same career opportunities. However, there are limited data on the range and specifics of potential barriers that withhold people in headache medicine and science from reaching their full potential. Moreover, people from different geographical regions often perceive different challenges. We aimed to identify world-wide perceived career barriers and possibilities for promoting equality amongst professionals in the headache fields. METHODS: A cross-sectional online survey was conducted among professionals in the field of headache globally. The questions of the survey were aimed at assessing perceived career barriers in four domains: professional recognition, opportunities in scientific societies, clinical practice, and salary and compensation. Perceived mentorship was also assessed. RESULTS: In total 580 responders completed the survey (55.3% women). Gender was the most important perceived barrier in almost all domains. Additionally, country of birth emerged as an important barrier to participation in international scientific societies. Career barriers varied across world regions. CONCLUSION: It is essential that longstanding and ongoing disparities by gender and country of origin for professionals in the headache field are globally acknowledged and addressed in areas of recruitment, retention, opportunities, mentor- and sponsorships, and advancement.

Dehydration and Headache.

PURPOSE OF REVIEW: We define dehydration and its relationship to pain physiology including both primary and secondary headache disorders. RECENT FINDINGS: Intravenous fluids administered for acute migraine attacks in an emergency department setting have not been shown to improve pain outcomes. However, increased intravascular volume before diagnostic lumbar puncture may reduce the frequency of post-lumbar puncture headache from iatrogenic spinal fluid leak. Maintenance of euhydration can help treat orthostatic and "coat-hanger" headache due to autonomic disorders. Similarly, prevention of fluid losses can mitigate secondary headaches provoked by dehydration such as cerebral venous thrombosis or pituitary apoplexy. Dehydration alone may cause headache, but oftentimes exacerbates underlying medical conditions such as primary headache disorders or other conditions dependent on fluid balance.

Narrative review of neuroimaging in migraine with aura.

OBJECTIVE: To improve the understanding of the role and utility of various neuroimaging modalities (clinical and research) for the evaluation of migraine aura (MA) and hemiplegic migraine during the ictal and interictal phases. BACKGROUND: MA is defined by reversible neurologic symptoms and is considered a manifestation of a primary condition. As such, most patients with MA do not require imaging. However, if there are atypical features, change in symptom pattern, or it is a first-time presentation, neuroimaging may be used to evaluate for secondary conditions. Neuroimaging includes many modalities, and it is important to consider what information is being captured by these modalities (i.e., structural vs. functional). Imaging abnormalities may be noted both during (ictal) and between (interictal) MA attacks, and it is important for clinicians to be familiar with neuroimaging findings reported in migraine with aura (MWA) compared with other conditions. METHODS: With the assistance of a medical librarian, we performed a review of the literature pertaining to MWA and neuroimaging in PubMed. Search terms included were magnetic resonance imaging, positron-emission tomography, single photon-emission computed tomography, functional magnetic resonance imaging, and migraine with aura. We hand-searched these references to inform our subsequent literature review. RESULTS: Acute MA can be associated with several unique neuroimaging findings-reversible cortical diffusion restriction, cortical venous engorgement, and a "biphasic" transition from hypoperfusion to hyperperfusion. Imaging findings during MA tend to span more than one vascular territory. Between acute attacks, neuroimaging in people with MWA can resemble migraine without aura in terms of white matter abnormalities and "infarct-like lesions." Research imaging modalities such as volumetric analysis and functional imaging have demonstrated unique findings in migraine with aura. CONCLUSION: Although migraine is a clinical diagnosis, understanding of neuroimaging findings in MWA can help clinicians interpret imaging findings and improve patient care.

Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-analysis.

Importance: Migraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy. Objective: To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults. Data Sources: Multiple databases from database inception to February 24, 2021. Study Selection: Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks. Data Extraction and Synthesis: Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small. Main Outcomes and Measures: The main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Findings: Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham. Conclusions and Relevance: There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.

Grand rounds education in neurology, with a focus on headache medicine.

OBJECTIVE: To quantify the proportion of headache-related grand rounds in academic neurology programs and to compare this with adult neurology residency director views on the need for an increase in headache-related grand rounds. BACKGROUND: Although headache are among the most prevalent and most burdensome neurologic conditions, headache medicine is often considered underrepresented in neurology departments. Additionally, prior studies have shown that many neurology residency directors feel that training programs do not include an adequate amount of exposure to headache clinics or headache-related didactics. One important aspect of didactic education in neurology departments is adult neurology grand rounds. Previous publications have evaluated neither the proportion of headache-related grand rounds in academic neurology departments nor the residency program directors' views on appropriate amount of headache-related grand rounds. Our study has attempted to quantify this information to elucidate opportunities to improve practice educational gaps. METHODS: In this cross-sectional study, we surveyed adult neurology residency directors (from the Accreditation Council for Graduate Medical Education [ACGME] listing of academic adult neurology residency programs) between October 2018 and September 2019. In addition, we used two methods to obtain the proportion of headache-related grand rounds in neurology: (1) emailing residency directors a questionnaire asking for a list of prior grand rounds topics and (2) an online search for each academic neurology program. RESULTS: First, for our grand rounds analysis, headache medicine consisted of 3.7% of the lectures in 2017-2018 and 6.3% of the lectures in 2018-2019 (average of each institution; 17 institutions and 411 total lectures in 2017-2018, 21 institutions and 463 total lectures in 2018-2019). The most common number of lectures on headache medicine for each grand rounds series was zero (for 7 of 17 grand rounds series in 2017-2018 and 7 of 21 in 2018-2019), followed closely by one lecture (for 6 of 17 grand rounds series in 2017-2018 and 6 of 21 in 2018-2019). Second, for our survey, the response rate was 19.3% (29/150). No residency director thought their institution had too many grand rounds dedicated to headache medicine, and 62.1% (18/29) thought they had an adequate amount of headache grand rounds. Within the survey responders, 75.9% (22/29) of adult neurology residency programs have a board-certified headache specialist at their institution. CONCLUSIONS: Although most adult neurology residency directors believe that headache is adequately represented in adult neurology grand rounds, headache medicine makes up 4%-6% of all neurology grand rounds. Compared with other neurology subspecialties and the other core ACGME milestones, headache makes up the fewest grand rounds lectures that were assessed in this study.