The call of the final frontier?

The target article is focused on locating the popularity of imaginary worlds in our adaptations for exploration. This commentary touches on developmental influences, vicarious enjoyment, the challenging of societal mores, plot, and whether men and women are drawn to the same features in the same ways.

Polypharmacy and comorbidities during pregnancy in a cohort of women with migraine.

OBJECTIVE: To describe longitudinal patterns of medication use throughout pregnancy in women with migraine. METHODS: We used the IBM MarketScan healthcare claims database in the US to create a cohort of pregnancies enrolled between 2011-2015 resulting in live or stillbirth. Migraine headache was identified based on ICD-9-CM diagnosis codes or procedure codes recorded in clinical encounters. Outcomes were patterns of prescriptions filled for medications that may be used to prevent migraine (antiepileptics, antihypertensives, antidepressants) or treat acute episodes (opioids, triptans, acetaminophen) and of other comorbid conditions (hypertension, psychiatric diagnoses, epilepsy). We used group-based multi-trajectory models to cluster women into similar longitudinal patterns of prescription fills. RESULTS: Of 859,501 pregnancies, 8168 had migraine. Within migraineurs, before pregnancy, the most commonly filled prescription was for a triptan (43.2%), followed by opioids (26.7%), acetaminophen (26.2%), antidepressants (24.9%), antiepileptics (18.6%) and antihypertensives (12.3%). Antiepileptics, antidepressants, and triptans were frequently discontinued early in pregnancy with few new users, while antihypertensives were discontinued by some users, but continued or initiated by a minority of users late in pregnancy. Opioids and acetaminophen were used intermittently throughout pregnancy. Comorbidities included hypertension (10.8%), epilepsy (4.7%), depression (14.0%), and anxiety (15.6%). Polypharmacy involving both preventive and acute medications was most common before pregnancy (31.4%) and declined in first trimester (14.7%). In all, 25.9% of women filled prescriptions for two or more acute medications before pregnancy. CONCLUSIONS: Medication use patterns during pregnancy for women with migraine are complex. Patterns of polypharmacy and comorbidity during pregnancy highlight an under-studied area relevant for maternal and child health outcomes.

Identification of work accommodations and interventions associated with work productivity in adults with migraine: A scoping review.

OBJECTIVE: To identify factors associated with work productivity in adults with migraine, and accommodations or interventions to improve productivity or the workplace environment for them. METHODS: We conducted a scoping review by searching MEDLINE, Embase, PsycINFO, Cumulative Index of Nursing and Allied Heath Literature, and Web of Science from their inception to 14 October 2019 for studies of any design that assessed workplace productivity in adults with migraine. RESULTS: We included 26 articles describing 24 studies after screening 4139 records. Five prospective cohort studies showed that education on managing migraine in the workplace was associated with an increase in productivity of 29-36%. Two studies showed that migraine education and management in the workplace were associated with increased productivity (absenteeism decreased by 50% in one study). One prospective cohort study showed that occupational health referrals were associated with more than 50% reduction in absenteeism. Autonomy, social support, and job satisfaction were positively associated with productivity, while quantitative demands, emotional demands, job instability, and non-conducive work environment triggers are negatively associated with productivity in workers with migraine. CONCLUSION: Despite migraine being the second leading cause of disability worldwide, there is a paucity of strong data on migraine-related work factors associated with productivity.Registration: None (scoping review).

The prevalence and impact of migraine and severe headache in the United States: Updated age, sex, and socioeconomic-specific estimates from government health surveys.

BACKGROUND AND OBJECTIVES: Accurate, up-to-date estimates of the burden of migraine and severe headache are important for evidence-based decision-making about workforce needs and the distribution of health resources. We used data from US government health surveys to report the prevalence, trends, and impact of this condition by age, sex, and poverty status. METHODS: We identified the most recent, publicly available summary statistics from the National Hospital Ambulatory Medical Care Survey, the National Ambulatory Medical Care Survey, and the National Health Interview Survey. We extracted and compiled relevant information from each study, with an emphasis on sex, age, and economic-related statistics. RESULTS: The age-adjusted prevalence of migraine and severe headache in the United States has remained stable over many years. In 2018, the age-adjusted prevalence was 15.9% across all adults. The sex ratio also remains stable, with 21% of women and 10.7% of men affected. Migraine continues to be an important public health problem, accounting for roughly 4 million emergency department (ED) visits in 2016, when headache was the fifth most common reason for an ED visit overall and the third most common reason for ED visits in females 15-64. Migraine also accounted for over 4.3 million office visits. Many adults with migraine or severe headaches are disadvantaged. In 2018, for example, roughly 40% of US adults with migraine were unemployed, and a similar proportion were classified as poor or "near poor." Roughly one in five had no health insurance and about a third had a high school education or less. CONCLUSIONS: Migraine and severe headaches are a serious public health issue in the United States, with the highest impact in women of childbearing age and those of lower socioeconomic status. Socioeconomic disadvantages also are highly prevalent among those with headaches. The economic consequences of the current coronavirus pandemic are likely to exacerbate all of these inequities. Increased attention to this high impact chronic pain condition, and improved funding for treatment provision and research, are warranted to reduce the future burden of disease.

The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice.

OBJECTIVE: To incorporate recent research findings, expert consensus, and patient perspectives into updated guidance on the use of new acute and preventive treatments for migraine in adults. BACKGROUND: The American Headache Society previously published a Consensus Statement on the use of newly introduced treatments for adults with migraine. This update, which is based on the expanded evidence base and emerging expert consensus concerning postapproval usage, provides practical recommendations in the absence of a formal guideline. METHODS: This update involved four steps: (1) review of data about the efficacy, safety, and clinical use of migraine treatments introduced since the previous Statement was published; (2) incorporation of these data into a proposed update; (3) review and commentary by the Board of Directors of the American Headache Society and patients and advocates associated with the American Migraine Foundation; (4) consideration of these collective insights and integration into an updated Consensus Statement. RESULTS: Since the last Consensus Statement, no evidence has emerged to alter the established principles of either acute or preventive treatment. Newly introduced acute treatments include two small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (ubrogepant, rimegepant); a serotonin (5-HT1F ) agonist (lasmiditan); a nonsteroidal anti-inflammatory drug (celecoxib oral solution); and a neuromodulatory device (remote electrical neuromodulation). New preventive treatments include an intravenous anti-CGRP ligand monoclonal antibody (eptinezumab). Several modalities, including neuromodulation (electrical trigeminal nerve stimulation, noninvasive vagus nerve stimulation, single-pulse transcranial magnetic stimulation) and biobehavioral therapy (cognitive behavioral therapy, biofeedback, relaxation therapies, mindfulness-based therapies, acceptance and commitment therapy) may be appropriate for either acute and/or preventive treatment; a neuromodulation device may be appropriate for acute migraine treatment only (remote electrical neuromodulation). CONCLUSIONS: The integration of new treatments into clinical practice should be informed by the potential for benefit relative to established therapies, as well as by the characteristics and preferences of individual patients.

Learning the full impact of migraine through patient voices: A qualitative study.

OBJECTIVE: To better characterize the ways that migraine affects multiple domains of life. BACKGROUND: Further understanding of migraine burden is needed. METHODS: Adults with migraine randomized to mindfulness-based stress reduction or headache education arms (n = 81) in two separate randomized clinical trials participated in semistructured in-person qualitative interviews conducted after the interventions. Interviews queried participants on migraine impact on life and were audio-recorded, transcribed, and summarized into a framework matrix. A master codebook was created until meaning saturation was reached and magnitude coding established code frequency. Themes and subthemes were identified using a constructivist grounded theory approach. RESULTS: Despite most participants being treated with acute and/or prophylactic medications, 90% (73/81) reported migraine had a negative impact on overall life, with 68% (55/81) endorsing specific domains of life impacted and 52% (42/81) describing impact on emotional health. Six main themes of migraine impact emerged: (1) global negative impact on overall life; (2) impact on emotional health; (3) impact on cognitive function; (4) impact on specific domains of life (work/career, family, social); (5) fear and avoidance (pain catastrophizing and anticipatory anxiety); and (6) internalized and externalized stigma. Participants reported how migraine (a) controls life, (b) makes life difficult, and (c) causes disability during attacks, with participants (d) experiencing a lack of control and/or (e) attempting to push through despite migraine. Emotional health was affected through (a) isolation, (b) anxiety, (c) frustration/anger, (d) guilt, (e) mood changes/irritability, and (f) depression/hopelessness. Cognitive function was affected through concentration and communication difficulties. CONCLUSIONS: Migraine has a global negative impact on overall life, cognitive and emotional health, work, family, and social life. Migraine contributes to isolation, frustration, guilt, fear, avoidance behavior, and stigma. A greater understanding of the deep burden of this chronic neurological disease is needed to effectively target and treat what is most important to those living with migraine.

Real-world effectiveness and tolerability of erenumab: A retrospective cohort study.

BACKGROUND: We aimed to systematically assess the effectiveness and tolerability of erenumab in a clinical setting, specifically a tertiary headache center. METHODS: This was a retrospective cohort study at the John Graham Headache Center of Brigham and Women's Hospital. All patients who received erenumab from a headache specialist at the Center from 17 May 2018 to 31 January 2019 were included. Patients were contacted and underwent a structured clinical interview including information about erenumab use, perceived benefit, adverse events (AEs), and a global assessment of benefit versus drawbacks. Chart review was performed for patients who could not be contacted. RESULTS: Four hundred and forty-four patients were initially identified and 418 were eligible. Two hundred and ninety-five participants completed the structured clinical interview portion of the study (response rate 70.6%). Seventy-four patient charts were additionally reviewed. Two hundred and forty-one participants had used erenumab. One hundred and sixty nine (70%) of participants experienced at least one adverse event, with constipation (43%), injection site reaction (24%), fatigue (15%), worsening headache (12%), and dizziness (11%) the five most commonly reported AEs. One hundred and sixty-eight participants (69.7%) felt that the benefits of erenumab outweighed any drawbacks. One hundred and fifty-one participants (62.7%) planned to continue using erenumab. Cost of treatment was cited by 12% of participants as a reason for either not starting or for stopping erenumab. Of patients who had an increase in dose due to lack of or partial efficacy, 46.5% felt that the dose increase was helpful. We identified one case of unintended pregnancy in our study population. CONCLUSIONS: This large "real-world" study validates the findings of benefit of erenumab observed in clinical trials. Although adverse events were far more common in this population than in clinical trials, the planned continuation rate was relatively high. The substantial discrepancy between adverse events seen in clinical practice compared with clinical trials suggests systematic differences between clinical trial participants and patients who receive the treatment in clinical practice, or may indicate suboptimal ascertainment of adverse events in the trials. Clinicians should continue to be vigilant for adverse events in clinical practice.

Epidemiology and Treatment of Menstrual Migraine and Migraine During Pregnancy and Lactation: A Narrative Review.

The peak prevalence of migraine occurs in women of reproductive age, and women experience a higher burden of migraine symptoms and disability compared to men. This increased burden of migraine in women is related to both developmental and temporally variable activational effects of female sex hormones. Changing levels of female sex hormones affect the expression of migraine during pregnancy, and, to a lesser degree, lactation, and are the mechanism underlying menstrual migraine. This review describes the evidence for sex differences in the expression of migraine across the reproductive epoch; reviews the epidemiology of migraine during pregnancy, lactation, and menses; and summarizes the available evidence for safety and efficacy of acute treatments during pregnancy and lactation and for menstrual migraine. Areas of controversy in treatment of migraine during pregnancy, including the use of magnesium, triptans vs butalbital combination medications, and onabotulinum toxin, are also explored.

Evidence Regarding Medication Overuse Headache in Children and Adolescents: Protocol for a Systematic Review.

OBJECTIVES: This proposed systematic review will identify the existing evidence on medication-overuse headache in children and adolescents. BACKGROUND: A number of medications have been shown to be effective for acute treatment of migraine in children and adolescents. However, patients may find they need to use their acute medications more frequently when migraine frequency is high. This has led to concern about their potential to develop medication-overuse headache. METHODS: We will search PubMed, Embase, Web of Science, PsycINFO, and Cochrane databases from their inception to present time. We will also search conference proceedings of the last 4 scientific meetings of relevant societies and scan the reference lists of studies identified through the search. Study designs will include case series, cross-sectional, cohort, case-control, and interventional studies. Participants will include children and adolescents under 18 years of age with primary headache disorders. We aim to determine whether frequency of acute medication use is associated with headache frequency in children and adolescents. Outcomes of interest include: (1) headache frequency; (2) change in headache frequency, with time and in relationship to use of acute medications; and (3) headache-related disability. We will also review data addressing treatment/management of medication overuse or medication-overuse headache in children and adolescents. Relevant comparators will be withdrawal vs reduction of acute medication, initiation of preventive therapy vs no initiation with or without withdrawal of acute medication, and initiation of preventive therapy early vs late. Outcomes of interest include (1) days of acute medication use; (2) headache frequency; (3) change in headache frequency; and (4) headache-related disability. After screening for inclusion, 2 team members will independently review and extract relevant data, and any discrepancies will be resolved through discussion and arbitration. We will assess risk of bias using appropriate tools (Cochrane Risk of Bias for randomized controlled trials (RCT) and Newcastle-Ottawa Score for observational studies). Data will be summarized descriptively in text and tables. RESULTS: This systematic review will provide an overview of the available evidence on medication-overuse headache in children and adolescents. CONCLUSIONS: Findings from this review will aid clinicians by clarifying for them the current state of the evidence base, and will inform design of future research on this topic.

Neuroimaging for Migraine: The American Headache Society Systematic Review and Evidence-Based Guideline.

OBJECTIVE: To provide updated evidence-based recommendations about when to obtain neuroimaging in patients with migraine. METHODS: Articles were included in the systematic review if they studied adults 18 and over who were seeking outpatient treatment for any type of migraine and who underwent neuroimaging (MRI or CT). Medline, Web of Science, and Cochrane Clinical Trials were searched from 1973 to August 31, 2018. Reviewers identified studies, extracted data, and assessed the quality of the evidence in duplicate. We assessed study quality using the Newcastle-Ottawa Scale. RESULTS: The initial search yielded 2269 publications. Twenty three articles met inclusion criteria and were included in the final review. The majority of studies were retrospective cohort or cross-sectional studies. There were 4 prospective observational studies. Ten studies evaluated the utility of CT only, 9 MRI only, and 4 evaluated both. Common abnormalities included chronic ischemia or atrophy with CT and MRI scanning, and non-specific white matter lesions with MRI. Clinically meaningful abnormalities requiring intervention were relatively rare. Clinically significant neuroimaging abnormalities in patients with headaches consistent with migraine without atypical features or red flags appeared no more common than in the general population. RECOMMENDATIONS: There is no necessity to do neuroimaging in patients with headaches consistent with migraine who have a normal neurologic examination, and there are no atypical features or red flags present. Grade A Neuroimaging may be considered for presumed migraine for the following reasons: unusual, prolonged, or persistent aura; increasing frequency, severity, or change in clinical features, first or worst migraine, migraine with brainstem aura, migraine with confusion, migraine with motor manifestations (hemiplegic migraine), late-life migraine accompaniments, aura without headache, side-locked headache, and posttraumatic headache. Most of these are consensus based with little or no literature support. Grade C.

The Prevalence and Impact of Migraine and Severe Headache in the United States: Figures and Trends From Government Health Studies.

BACKGROUND AND OBJECTIVES: In this targeted systematic review, we aimed to identify up-to-date prevalence estimates of migraine and severe headache in adults from population-based US government surveys. Our goal was to assess the stability of prevalence estimates over time, and to identify additional information pertinent to the burden and treatment of migraine and other severe headache conditions. METHODS: We searched for the most current publicly available summary statistics from the National Health Interview Survey (NHIS), the National Hospital Ambulatory Medical Care Survey (NHAMCS), and the National Ambulatory Medical Care Survey (NAMCS). We extracted and summarized data from each study over time and as a function of demographic variables. RESULTS: The prevalence and burden of self-reported migraine and severe headache in the US adult population is high, affecting roughly 1 out of every 6 American and 1 in 5 women over a 3-month period (15.3% overall [95% CI 14.75-15.85], 9.7% of males [95% CI 9.05-10.35] and 20.7% of females [95% CI 19.84-21.56]). The prevalence has been remarkably stable over a period of 19 years. The prevalence of migraine or severe headache in 2015 was highest in American Indian or Alaska Natives (18.4%) compared with whites, blacks, or Hispanics, with the lowest prevalence in Asians (11.3%). There is a higher burden of migraine in those aged 18-44 (17.9%), people who are unemployed (21.4%), those with family income less than $35,000 per year (19.9%), and the elderly and disabled (16.4%). Headache is consistently the fourth or fifth most common reason for visits to the emergency department, accounting for roughly 3% of all emergency department visits annually. In reproductive aged women, headache is the third leading cause of emergency department visits. CONCLUSIONS: Severe headache and migraine remain important public health problems that are more common and burdensome for women, particularly women of childbearing age, and other historically disadvantaged segments of the population. These inequities could be exacerbated if new high-cost treatments are inaccessible to those who need them most.

Safety Problems With a Transdermal Patch for Migraine: Lessons From the Development, Approval, and Marketing Process.

OBJECTIVE: We sought to analyze publicly available information about patient harm associated with an iontophoretic sumatriptan patch, to identify what went wrong and to suggest ways in which similar problems might be prevented in the future. BACKGROUND: The Zecuity® sumatriptan iontophoretic transdermal system was marketed for acute treatment of migraine. The patch was withdrawn less than 10 months after its introduction because of multiple reports of scarring and burning. As of 2018, the FDA Adverse Event Reporting System public dashboard lists a total of 2889 reports of safety problems with the patch, 904 of which were classified as serious. METHODS: For this narrative review, we examined US Food and Drug Administration documents related to the new drug application for this product and its approval. We searched Clinicaltrials.gov, PubMed, Google, Facebook, Twitter, and Instagram public posts for relevant information relating to the patch, its approval, marketing, and complications. RESULTS: The FDA knew about problems with burns and scarring prior to approval of the product, and turned down the initial new drug application for this reason and because of other quality problems with the patch. The reapplication was approved despite continued concerns of several FDA reviewers about safety. The approval required the manufacturer to comply with enhanced postmarketing safety reporting. However, product information and labeling did not mention the possibility of burns or scarring. Approval was based on 1 clinical trial and 2 open label studies in which reporting of adverse events was suboptimal. The clinical trials had been prospectively registered but outcomes had been changed around the time the trial concluded. Aggressive marketing efforts and social media activity may have contributed to inaccurate perceptions of safety and efficacy, but social media also provided a written and photographic record of burns and other harm suffered by patients who used the patch. CONCLUSIONS: Our review identified several problems with the development, testing, approval, and marketing of the Zecuity patch. To improve the process of developing headache treatments, it is important to consider the lessons that can be drawn from an examination of this high-profile failure of the drug development and regulatory system.

Risk of Stroke Associated With Use of Estrogen Containing Contraceptives in Women With Migraine: A Systematic Review.

OBJECTIVE: Migraine with aura has been associated with increased risk of ischemic and hemorrhagic stroke. Prior studies have shown a further increase in risk in women using combined hormonal contraceptives (CHCs). This has led to guidelines recommending against use of CHCs in this population. We sought to assess whether the risk of stroke is associated with the dose of estrogen and whether there is evidence of synergism between migraine and CHCs. We also sought to assess whether an interaction effect exists between migraine and CHCs. METHODS: We searched PubMed, the Cochrane Library, and EMBASE from inception through January 2016 for relevant English-language studies of adults, of any design. We included studies that examined exposure to CHCs and reported outcomes of ischemic or hemorrhagic stroke. Data extraction and assessment of study quality were conducted independently by reviewer pairs and quality was assessed with the GRADE and Newcastle Ottawa scales. RESULTS: Of 2480 records, 15 studies met inclusion criteria and six provided odds ratios for the relevant population. The point estimates for the odds ratios for ischemic stroke in women with migraine who used CHCs with any dose of estrogen ranged from 2.08 to 16.9. Studies were generally small and confidence intervals were wide. No studies reported odds ratios for stroke risk as a function of estrogen dose in women with migraine, largely due to insufficient sample sizes. No interaction effect between migraine and CHCs was seen in the seven studies that assessed this. One study differentiated risk by presence or absence of migraine aura and found an increased risk in the migraine with aura population (OR 6.1; CI 3.1 to 12.1 in migraine with aura vs 1.8; CI 1.1 to 2.9 in the migraine without aura group). Studies generally had high Newcastle Ottawa scores and low GRADE levels of evidence. No studies met all three supplementary quality criteria (assessed migraine subtype, used International Classification of Headache Disorders criteria for diagnosis of migraine, and stratified risk by estrogen dose). CONCLUSIONS: This systematic review shows a lack of good quality studies assessing risk of stroke associated with low dose estrogen use in women with migraine. Further study in this area is needed. The available evidence is consistent with an additive increase in stroke risk with CHC use in women with migraine with aura. Since the absolute risk of stroke is low even in the presence of these risk factors, use of CHCs in women who have migraine with aura should be based on an individualized assessment of harms and benefits.

Episodic Migraine With and Without Aura: Key Differences and Implications for Pathophysiology, Management, and Assessing Risks.

PURPOSE OF REVIEW: To review the pathophysiologic, epidemiologic, and clinical evidence for similarities and differences between migraine with and without aura. RECENT FINDINGS: The ICHD-3 has recently refined the diagnostic criteria for aura to include positive symptomatology, which better differentiates aura from TIA. Although substantial evidence supports cortical spreading depression as the cause of visual aura, the role (if any) of CSD in headache pain is not well understood. Recent imaging evidence suggests a possible hypothalamic origin for a headache attack, but further research is needed. Migraine with aura is associated with a modest increase in the risk of ischemic stroke. The etiology for this association remains unclear. There is a paucity of evidence regarding treatments specifically aimed at the migraine with aura subtype, or whether migraine with vs without aura responds to treatment differently. Migraine with typical aura is therefore often treated similarly to migraine without aura. Lamotrigine, daily aspirin, and flunarizine have evidence for efficacy in prevention of migraine with aura, and magnesium, ketamine, furosemide, and single-pulse transcranial magnetic stimulation have evidence for use as acute treatments. Although triptans have traditionally been contraindicated in hemiplegic migraine and migraine with brainstem aura, this prohibition is being reconsidered in the face of evidence suggesting that use may be safe. The debate as to whether migraine with and without aura are different entities is ongoing. In an era of sophisticated imaging, genetic advancement, and ongoing clinical trials, efforts to answer this question are likely to yield important and clinically meaningful results.

Potential predatory and legitimate biomedical journals: can you tell the difference? A cross-sectional comparison.

BACKGROUND: The Internet has transformed scholarly publishing, most notably, by the introduction of open access publishing. Recently, there has been a rise of online journals characterized as 'predatory', which actively solicit manuscripts and charge publications fees without providing robust peer review and editorial services. We carried out a cross-sectional comparison of characteristics of potential predatory, legitimate open access, and legitimate subscription-based biomedical journals. METHODS: On July 10, 2014, scholarly journals from each of the following groups were identified - potential predatory journals (source: Beall's List), presumed legitimate, fully open access journals (source: PubMed Central), and presumed legitimate subscription-based (including hybrid) journals (source: Abridged Index Medicus). MEDLINE journal inclusion criteria were used to screen and identify biomedical journals from within the potential predatory journals group. One hundred journals from each group were randomly selected. Journal characteristics (e.g., website integrity, look and feel, editors and staff, editorial/peer review process, instructions to authors, publication model, copyright and licensing, journal location, and contact) were collected by one assessor and verified by a second. Summary statistics were calculated. RESULTS: Ninety-three predatory journals, 99 open access, and 100 subscription-based journals were analyzed; exclusions were due to website unavailability. Many more predatory journals' homepages contained spelling errors (61/93, 66%) and distorted or potentially unauthorized images (59/93, 63%) compared to open access journals (6/99, 6% and 5/99, 5%, respectively) and subscription-based journals (3/100, 3% and 1/100, 1%, respectively). Thirty-one (33%) predatory journals promoted a bogus impact metric - the Index Copernicus Value - versus three (3%) open access journals and no subscription-based journals. Nearly three quarters (n = 66, 73%) of predatory journals had editors or editorial board members whose affiliation with the journal was unverified versus two (2%) open access journals and one (1%) subscription-based journal in which this was the case. Predatory journals charge a considerably smaller publication fee (median $100 USD, IQR $63-$150) than open access journals ($1865 USD, IQR $800-$2205) and subscription-based hybrid journals ($3000 USD, IQR $2500-$3000). CONCLUSIONS: We identified 13 evidence-based characteristics by which predatory journals may potentially be distinguished from presumed legitimate journals. These may be useful for authors who are assessing journals for possible submission or for others, such as universities evaluating candidates' publications as part of the hiring process.

PFO and Migraine: Is There a Role for Closure?

Observational studies suggest that closure of a patent foramen ovale for other indications may reduce or even eliminate migraine attacks, particularly migraine with aura. The first randomized clinical trial of patent foramen ovale (PFO) closure for prevention of migraine, the MIST trial, showed negative results. The results of the other two completed studies in this area have recently been published in the last year. PRIMA and PREMIUM were also both negative for their primary endpoints. The PREMIUM trial did show a reduction in headache days in the migraine with aura subgroup but the final results of this subset analysis have not been published. There may be an as yet undetermined subgroup of patients with migraine who would benefit from closure, but slow recruitment has been a barrier to further study. Several potentially life-threatening procedure-related adverse events occurred in the clinical trials. At this time, we recommend against offering PFO closure as a preventive treatment for migraine. Based on available observational data, patients for whom PFO closure is indicated for other reasons may see some improvement in their migraines.