Pain medication beliefs in individuals with headache.

OBJECTIVE: To evaluate pain medication beliefs in a community sample of individuals with headache. BACKGROUND: Previous studies of medication adherence for individuals with headache have identified a high rate of prescription nonfulfillment, frequent medication discontinuation, and widely varying levels of medication-related satisfaction. Still, there is a limited understanding of how these individuals view their medications and their relationships with health-care providers. Insight into these perceptions could prove useful in explaining medication adherence behaviors. METHODS: In this secondary analysis of a cross-sectional study, data from N = 215 adults with headache were analyzed. Participants completed the Pain Medication Attitudes Questionnaire (PMAQ), Center for Epidemiologic Studies Depression Scale (CES-D), State-Trait Anxiety Inventory Form Y-2, Weekly Stress Inventory Short Form, and Migraine Disability Scale. These participants also provided a list of their current pain medications. RESULTS: Using the PMAQ, participants could be characterized as having medication beliefs that were "trusting and unconcerned" (n = 83/215 [38.6%]), "skeptical and somewhat worried" (n = 99/215 [46.0%]), or "skeptical and concerned" (n = 33/215 [15.3%]). Individuals with skeptical and concerned beliefs expressed elevated concerns (z > 1.15) about side effects, scrutiny, perceived need, tolerance, withdrawal, and addiction. Individuals who were trusting and unconcerned expressed low levels (z < -0.40) of these beliefs. Increasing levels of mistrust and medication concerns were correlated with higher depression scores on the CES-D, with values ranging from r = 0.23 to r = 0.38. CONCLUSIONS: Subgroups of pain medication beliefs were identified, including two groups of patients with at least some concerns about their medical providers. Beliefs ranged from a lack of concern about using pain medications to worries about scrutiny and harm. It is unclear if poor experiences with pain medications cause these beliefs or if they prevent individuals from effectively utilizing medications. Additionally, more negative beliefs about pain medications were associated with more depressive symptoms.

Learning headache triggers through experience: A laboratory study.

OBJECTIVE: To examine how individuals may learn headache trigger beliefs through sequential symbolic pairings of trigger candidates and headache attacks. BACKGROUND: Learning from experience may be a major source of information about headache triggers. Little is known about learning-based influences on the establishment of trigger beliefs. METHODS: This cross-sectional, observational study included N = 300 adults with headache who participated in a laboratory computer task. First, participants rated the chances (0%-100%) that encountering specific triggers would lead to experiencing a headache. Then, 30 sequential images with the presence or absence of a common headache trigger were presented alongside images representing the presence or absence of a headache attack. The primary outcome measure was the cumulative association strength rating (0 = no relationship to 10 = perfect relationship) between the trigger and headache using all previous trials. RESULTS: A total of N = 296 individuals completed 30 trials for each of three triggers, yielding 26,640 total trials for analysis. The median [25th, 75th] association strength ratings for each of the randomly presented headache triggers were 2.2 [0, 3] for the Color Green, 2.7 [0, 5] for Nuts, and 3.9 [0, 8] for Weather Changes. There was a strong association between the "true" cumulative association strength and corresponding ratings. A 1-point increase on the phi scale (i.e., no relationship to perfect relationship) was associated with a 1.20 (95% CI: 0.81 to 1.49, p < 0.0001) point increase in association strength rating. A participant's prior belief about the potency of a trigger affected their perceived rating of the accumulating evidence, accounting for 17% of the total variation. CONCLUSION: In this laboratory task, individuals appeared to learn trigger-headache associations through repeated exposures to accumulating symbolic evidence. Prior beliefs about the triggers appeared to influence ratings of the strength of relationships between triggers and headache attacks.

Information theory and headache triggers.

OBJECTIVES: This secondary analysis evaluated the information content exhibited by various measurement strategies of commonly perceived causes, or "triggers," of headache attacks. BACKGROUND: When evaluating triggers of primary headache attacks, the variation observed in trigger candidates must be measured to compare against the covariation in headache activity. Given the numerous strategies that could be used to measure and record headache trigger variables, it is useful to consider the information contained in these measurements. METHODS: Using previously collected data from cohort and cross-sectional studies, online data sources, and simulations, the Shannon information entropy exhibited by many common triggers was evaluated by analyzing available time-series or theoretical distributions of headache triggers. The degree of information, reported in bits, was compared across trigger variables, measurement strategies, and settings. RESULTS: A wide range of information content was observed across headache triggers. Due to lack of variation, there was little information, near 0.00 bits, in triggers like red wine and air conditioning. Most headache triggers exhibited more information when measured using an ordinal scale of presence/degree (e.g., absent, mild, moderate, severe) versus a present/absent binary coding. For example, the trigger "joy" exhibited 0.03 bits when assessed using binary coding but 1.81 bits when coded using an ordinal scale. More information was observed with the use of count data (0.86 to 1.75 bits), Likert rating scales (1.50 to 2.76 bits), validated questionnaires (3.57 to 6.04 bits), weather variables (0.10 to 8.00 bits), and ambulatory monitoring devices (9.19 to 12.61 bits). CONCLUSIONS: Although commonly used, all binary-coded measurements contain ≤1.00 bit of information. Low levels of information in trigger variables make associations with headache activity more difficult to detect. Assessments that balance information-rich measurements with reasonable participant burden using efficient formats (e.g., Likert scales) are recommended to enhance the evaluation of the association with headache activity.

Clinical features of new daily persistent headache: A retrospective chart review of 328 cases.

OBJECTIVE: To describe the clinical features of new daily persistent headache (NDPH) at an outpatient neurology clinic with a subspecialty interest in headache in Houston, Texas. METHODS: A retrospective chart review was performed by a neurologist subspecialty certified in headache medicine of all patients seen from September 1, 2011 through February 28, 2020 (8.5 years) with a provisional diagnosis of NDPH and abstracted charts meeting criteria for primary NDPH. RESULTS: A total of 328 patients met the International Classification of Headache Disorders, 3rd edition criteria including 215 (65.5%) female patients. The mean age of onset was 40.3 years (range 12-87 years) with a mean age at first consultation in the study clinic of 42.6 years (range 12-87 years). The median [25th, 75th] duration of NDPH at initial consultation was 0.7 [0.3, 2.0] years, and at last visit, it was 1.9 [0.7, 4.8] years. The headaches were side-locked unilateral in 28/328 (8.5%). 12/328 cases (3.6%) with a thunderclap onset are reported. There was no obvious seasonal or other cyclical variation. The pain was usually moderate to severe and more often severe for the migraine phenotype (MP; 260/328 [79.3%] of cases) than for the tension-type phenotype (TTP). Precipitating factors were the following: stressful life events, 67/328 (20.4%); upper respiratory infection or flu-like illness, 33/328 (10.1%); and extracranial surgery, 5/328 (1.5%). Exacerbating or aggravating factors similar to migraine triggers were more often reported with the MP than with the TTP in this sample. For the MP, vertigo or dizziness was reported by 19/260 (7.3%) and a visual aura by 21/260 (8.1%) with descriptions provided. The prognostic types were the following for all patients: persisting (refractory), 305/328 (93.0%); relapsing-remitting, 9/328 (2.7%); and remitting (self-limited), 14/328 (4.3%). CONCLUSION: NDPH is typically of moderate to severe intensity often with migraine features without obvious seasonal or other cyclical variation. Most cases are refractory. 3.6% have a thunderclap onset often with a good response to treatment.

Continuous updating of individual headache forecasting models using Bayesian methods.

OBJECTIVE: To illustrate the benefits of deploying individual headache forecasting models using continuous updating with Bayesian methods. BACKGROUND: The ability to reliably forecast headache attacks within an individual over time would enhance the study of attacks and allow preemptive treatment. However, deploying a suitable forecasting model in a clinical setting will likely involve several unique challenges related to heterogeneity in the predictor weights, limited or sparse data, and the need for a quick "warm-up." The use of Bayesian methods offers solutions to each of these specific challenges. METHODS: This was a post hoc analysis of a cohort study of individuals with episodic migraine attacks. Individuals completed daily diaries that allowed the estimation of several forecasting models, each using different types of ancillary information incorporated into formal prior probability distributions. An in silico analysis was conducted that mimicked the deployment of these models in a clinical-like setting where the parameters of the models were continuously updated and evaluated each day using root mean square error (RMSE). RESULTS: Individuals (N = 95) were followed for 50 days and contributed 3359 days of nonmissing diary data. During the observation period, there were 1293/3359 (38.5%) days with a headache attack. Self-reported baseline headache frequency was associated with the corresponding predicted probability of future attacks, r = 0.15-0.39. At Day 25, the correlation between baseline information and predicted attack likelihood was r = 0.29 (95% CI: 0.09-0.47). Additionally, the use of prior probability distributions for model parameters improved the model fit, especially early in the deployment of the models (e.g., Day 5 RMSE 0.45 vs. 0.43). Models using informative prior probability distributions outperformed the models estimated without this information during the first 42 days of observation, although performance became more similar as more data were collected. CONCLUSIONS: This analysis demonstrates the value of Bayesian methods in using additional available information to improve forecasting model performance, especially early in the deployment of a forecasting model. To obtain the full value of such models or to apply any model in clinical settings, a model with adequate discrimination and calibration will be needed.

The Society for Obstetric Anesthesia and Perinatology Coronavirus Disease 2019 Registry: An Analysis of Outcomes Among Pregnant Women Delivering During the Initial Severe Acute Respiratory Syndrome Coronavirus-2 Outbreak in the United States.

BACKGROUND: Early reports associating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with adverse pregnancy outcomes were biased by including only women with severe disease without controls. The Society for Obstetric Anesthesia and Perinatology (SOAP) coronavirus disease 2019 (COVID-19) registry was created to compare peripartum outcomes and anesthetic utilization in women with and without SARS-CoV-2 infection delivering at institutions with widespread testing. METHODS: Deliveries from 14 US medical centers, from March 19 to May 31, 2020, were included. Peripartum infection was defined as a positive SARS-CoV-2 polymerase chain reaction test within 14 days of delivery. Consecutive SARS-CoV-2-infected patients with randomly selected control patients were sampled (1:2 ratio) with controls delivering during the same day without a positive test. Outcomes were obstetric (eg, delivery mode, hypertensive disorders of pregnancy, and delivery <37 weeks), an adverse neonatal outcome composite measure (primary), and anesthetic utilization (eg, neuraxial labor analgesia and anesthesia). Outcomes were analyzed using generalized estimating equations to account for clustering within centers. Sensitivity analyses compared symptomatic and asymptomatic patients to controls. RESULTS: One thousand four hundred fifty four peripartum women were included: 490 with SARS-CoV-2 infection (176 [35.9%] symptomatic) and 964 were controls. SARS-CoV-2 patients were slightly younger, more likely nonnulliparous, nonwhite, and Hispanic than controls. They were more likely to have diabetes, obesity, or cardiac disease and less likely to have autoimmune disease. After adjustment for confounders, individuals experiencing SARS-CoV-2 infection exhibited an increased risk for delivery <37 weeks of gestation compared to controls, 73 (14.8%) vs 98 (10.2%) (adjusted odds ratio [aOR], 1.47; 95% confidence interval [CI], 1.03-2.09). Effect estimates for other obstetric outcomes and the neonatal composite outcome measure were not meaningfully different between SARS-CoV-2 patients versus controls. In sensitivity analyses, compared to controls, symptomatic SARS-CoV-2 patients exhibited increases in cesarean delivery (aOR, 1.57; 95% CI, 1.09-2.27), postpartum length of stay (aOR, 1.89; 95% CI, 1.18-2.60), and delivery <37 weeks of gestation (aOR, 2.08; 95% CI, 1.29-3.36). These adverse outcomes were not found in asymptomatic women versus controls. SARS-CoV-2 patients (asymptomatic and symptomatic) were less likely to receive neuraxial labor analgesia (aOR, 0.52; 95% CI, 0.35-0.75) and more likely to receive general anesthesia for cesarean delivery (aOR, 3.69; 95% CI, 1.40-9.74) due to maternal respiratory failure. CONCLUSIONS: In this large, multicenter US cohort study of women with and without peripartum SARS-CoV-2 infection, differences in obstetric and neonatal outcomes seem to be mostly driven by symptomatic patients. Lower utilization of neuraxial analgesia in laboring patients with asymptomatic or symptomatic infection compared to patients without infection requires further investigation.

Appraisal of Headache Trigger Patterns Using Calendars.

OBJECTIVE: Using experimental, yet realistic, headache calendars, this laboratory study evaluated the ability of individuals to identify the degree of association between triggers and headaches. BACKGROUND: Individuals with headache often record daily diaries or calendars to identify their patterns of triggers. METHODS: This cross-sectional, observational study included adults with migraine, tension-type, or cluster headache who had ever experienced more than 5 attacks. Participants (N = 300) were presented with headache calendars and asked to rate the strength of the relationship (how strongly one causes the other) between 3 experimental triggers (high stress, poor sleep, and cinnamon) and headache using a 0 ("no relationship") to 10 ("perfect relationship") scale for each calendar. RESULTS: Calendars with a high positive correlation between trigger and headache had higher participant ratings than those with low correlations. The median [25th, 75th] of ratings for each correlation level was low correlation: 1 [0, 4], medium: 4 [2, 5], and high: 5 [4, 8], P < .0001. However, participants appeared to ignore negative associations (ie, trigger present with no headache) and rated calendars with more headache days as having higher associations, regardless of the true relationship. The ratings for 2, 6, and 26 headache days were 1 [0, 3], 4 [1, 6], and 8 [0, 10], respectively (P < .0001). Participants' previous beliefs about the triggers also affected their ratings (average correlation across triggers: r = 0.25, P < .0001). CONCLUSIONS: This laboratory task supports the notion that individuals with headache are able to identify the association between headaches and triggers using headache calendars. However, these judgments can be biased by the individuals' previous beliefs about the trigger and by the degree of headache activity.

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.

Headache Triggers as Surprise.

OBJECTIVES: To examine the hypothesis that surprising experiences of headache triggers are associated with daily headache activity. BACKGROUND: Little is known about the specific environmental or behavioral interactions that might trigger a headache attack in a prone individual. We propose that headache trigger exposures can be usefully characterized, not only by their mechanisms of action, but also on the degree of "surprise" they present to the individual. This hypothesis is based on elements of information theory: that unusual events and experiences carry more information than common events and experiences and that headache attacks are associated with reactions to uncommon or unexpected biopsychosocial exposures. METHODS: A secondary analysis of the Headache Prediction Study, this prospective cohort study followed N = 95 individuals with episodic migraine who contributed 4195 days of diary data. Information was collected on daily levels of several common headache triggers: number of caffeinated beverages, number of alcoholic beverages, stress (Daily Stress Inventory), and mood disturbance (Profile of Mood States). The probability of observing variations in each trigger was used to estimate the "surprisal" of experiencing each trigger, and this information, measured in bits, was used to predict headache attacks. RESULTS: Participants experienced a headache attack on 1613 of 4195 days (38.5%). Each of the triggers was modestly related to the probability of experiencing a future headache in a complex manner that involved interactions between current headache status, current levels of the trigger, and lagged (previous) levels of the trigger. However, when expressed as a surprisal, the associations were simplified and strengthened. For example, each of the individual trigger surprisals exhibited a meaningful association with the development of a future headache attack (expressed as a 1 SD change in surprisal), with odds ratios ranging from a low of 1.11 (95%CI: 1.00 to 1.24) for alcohol to a high of 1.30 (95%CI: 1.14 to 1.46) for stress. The individual surprisals could be summed for total trigger surprise and exhibited a reliable association with new onset headache, OR 1.35 (95%CI: 1.17 to 1.49). This score exhibited superior discrimination between headache and non-headache days from all of the individual triggers (ignoring base rate, AUC: 0.61; AUC: 0.71 with base rate). CONCLUSIONS: Diverse headache triggers can be uniformly described using their probability distributions. Rare values of headache triggers, or surprising values, were found to have consistent associations with headache activity across a variety of triggers. This finding, if validated in external data using other triggers, has potential to be used to conceptualize the influence of a wide range of headache triggers.

Influences on headache trigger beliefs and perceptions.

Background Previous headache trigger studies have primarily utilized checklists to measure beliefs about triggers. While this work has defined the diversity of beliefs across headache sufferers, the strength of association and the frequency at which these triggers are encountered remain unexplored. Objective To measure the strength of association, frequency of encounter, and influences on trigger beliefs and perceptions using a laboratory assessment task. Methods This cross-sectional observational study, part of the HACOGS project, included adult current migraine, tension-type, or cluster headache sufferers. Participants rated the chances they would experience a headache if they were to encounter a specific trigger and the number of days per month they experience that trigger for 33 common triggers. Results All 300 participants contributed data on all triggers, with little missing data (1.2%). All triggers exhibited a high degree of inter-individual variability on the strength of association and encounter perceptions. Many triggers were perceived to be encountered daily (e.g., caffeine, air conditioning), and a full range of perceptions were observed for each trigger. Stress (75% chance of headache), missing a meal (60%), and dehydration (60%) were the triggers with the greatest potency beliefs. Only 8-15% of these beliefs were related to individual differences and 26-27% to the triggers themselves. Conclusions Participants expressed diverse beliefs and perceptions about the strength of many common headache triggers. Variation in these beliefs was not associated with individual differences or the triggers themselves. This finding supports the importance of measuring more than just the presence-absence of trigger beliefs.

Perceived triggers of primary headache disorders: A meta-analysis.

Objective To quantitatively synthesize extant literature on perceived triggers of primary headache disorders. Methods A meta-analytic review of headache trigger survey studies was conducted. Endorsement rates, assessment method, and headache and sample characteristics were extracted from included articles. Separate random-effects models were used to assess trigger endorsement rates and post-hoc meta-regressions examined potential moderator variables. Results 85 articles from 1958 to 2015 were included, involving 27,122 participants and querying 420 unique triggers (collapsed into 15 categories). Four-fifths (0.81; 95% CI .75 to .86) of individuals with migraine or tension-type headache endorsed at least one trigger. Rates increased with the number of categories queried (OR: 1.18, 1.08-1.30) and year of publication (OR: 1.04, 1.00-1.08). The triggers most commonly endorsed were stress (.58, .53-.63) and sleep (.41, .36-.47). Conclusions Extreme heterogeneity characterizes the headache trigger literature. Most individuals with a primary headache disorder perceive their attacks to be triggered by one or more precipitants, the most common of which are stress and sleep. However, trigger endorsement is influenced by method of assessment. Enhancing methodological consistency and prioritizing experimental studies would improve our understanding of headache triggers.

Reasons for Manuscript Rejection After Peer Review From the Journal Headache.

OBJECTIVE: To identify and characterize the reasons manuscripts are rejected after peer review from the journal Headache. BACKGROUND: Numerous editorials, reviews, and research manuscripts have been published on the topic of manuscript rejection. However, few of these papers evaluate the reasons for rejection after peer review systematically. None are specific to the field of neurology or headache medicine. METHODS: A retrospective analysis of all submissions to Headache from January 1, 2014 through December 31, 2016 was performed. Peer reviewer and editor comments for each manuscript were reviewed, and unlimited reasons for rejection were coded for each manuscript. Detailed reasons for rejection were then grouped into 9 broader categories. RESULTS: A total of 784 submissions were received from January 1, 2014 through December 31, 2016. Of those, 336 were immediately rejected and 434 went on to peer review. During this period, the overall rejection rate was 62.6% and the rejection rate after peer review was 35.7%. The 6 most common reasons for rejection after peer review were: flaws in methodology and study design, poor reporting of methodology, poor statistical analysis, overstatement of conclusions, problems with covariates or outcomes, and problems with the control or case group. CONCLUSION: Flaws in methodology and study design were the most common reasons for rejection after peer review from Headache between 2014-2016.

Forecasting Migraine Attacks and the Utility of Identifying Triggers.

PURPOSE OF REVIEW: This review synthesizes the utility of measuring migraine triggers for the purpose of forecasting future headache attacks. The nature of forecasting models, headache triggers as inputs to such models, and how these trigger exposures can be measured for forecasting are reviewed. A critical evaluation of the existing forecasting models in the context of their potential application for preemptive treatment is considered. RECENT FINDINGS: A substantial pool of candidate trigger factors could be considered in the creation of forecasting models. However, because mechanistic information about causal factors that precede a migraine attack is not well understood, and such factors are difficult to measure, empirical models that are based on trigger factors that are merely associated with the onset of headache activity are likely to be the focus of forecasting efforts in the near future. Of such factors, stress has considerable empirical support and has been used to successfully forecast future headache attacks within individuals over time. However, at present, existing models possess only modest levels of discrimination and lack strong resolution in generated predictions. Current headache forecasting models represent an important first step in accurately predicting future headache activity. However, to utilize these models in a preemptive treatment paradigm where the risk of headache is treated prior to the actual experience of pain, these models must achieve greater precision with good calibration and generate predictions that are clinically actionable by individuals in their real-time home environments.

Using Search Engines to Investigate Shared Migraine Experiences.

OBJECTIVES: To investigate migraine patterns in the United States using Google search data and utilize this information to better understand societal-level trends. Additionally, we aimed to evaluate time-series relationships between migraines and social factors. BACKGROUND: Extensive research has been done on clinical factors associated with migraines, yet population-level social factors have not been widely explored. Migraine internet search data may provide insight into migraine trends beyond information that can be gleaned from other sources. METHODS: In this longitudinal analysis of open access data, we performed a time-series analysis in which about 12 years of Google Trends data (January 1, 2004 to August 15, 2016) were assessed. Data points were captured at a daily level and Google's 0-100 adjusted scale was used as the primary outcome to enable the comparison of relative popularity in the migraine search term. We hypothesized that the volume of relative migraine Google searches would be affected by societal aspects such as day of the week, holidays, and novel social events. RESULTS: Several recurrent social factors that drive migraine searches were identified. Of these, day of the week had the most significant impact on the volume of Google migraine searches. On average, Mondays accumulated 13.31 higher relative search volume than Fridays (95% CI: 11.12-15.51, P ≤ .001). Surprisingly, holidays were associated with lower relative migraine search volumes. Christmas Day had 13.84 lower relative search volumes (95% CI: 6.26-21.43, P ≤ .001) and Thanks giving had 20.18 lower relative search volumes (95% CI: 12.55-27.82, P ≤ .001) than days that were not holidays. Certain novel social events and extreme weather also appear to be associated with relative migraine Google search volume. CONCLUSIONS: Social factors play a crucial role in explaining population level migraine patterns, and thus, warrant further exploration.

Forecasting Individual Headache Attacks Using Perceived Stress: Development of a Multivariable Prediction Model for Persons With Episodic Migraine.

OBJECTIVE: To develop and validate a prediction model that forecasts future migraine attacks for an individual headache sufferer. BACKGROUND: Many headache patients and physicians believe that precipitants of headache can be identified and avoided or managed to reduce the frequency of headache attacks. Of the numerous candidate triggers, perceived stress has received considerable attention for its association with the onset of headache in episodic and chronic headache sufferers. However, no evidence is available to support forecasting headache attacks within individuals using any of the candidate headache triggers. METHODS: This longitudinal cohort with forecasting model development study enrolled 100 participants with episodic migraine with or without aura, and N = 95 contributed 4626 days of electronic diary data and were included in the analysis. Individual headache forecasts were derived from current headache state and current levels of stress using several aspects of the Daily Stress Inventory, a measure of daily hassles that is completed at the end of each day. The primary outcome measure was the presence/absence of any headache attack (head pain > 0 on a numerical rating scale of 0-10) over the next 24 h period. RESULTS: After removing missing data (n = 431 days), participants in the study experienced a headache attack on 1613/4195 (38.5%) days. A generalized linear mixed-effects forecast model using either the frequency of stressful events or the perceived intensity of these events fit the data well. This simple forecasting model possessed promising predictive utility with an AUC of 0.73 (95% CI 0.71-0.75) in the training sample and an AUC of 0.65 (95% CI 0.6-0.67) in a leave-one-out validation sample. This forecasting model had a Brier score of 0.202 and possessed good calibration between forecasted probabilities and observed frequencies but had only low levels of resolution (ie, sharpness). CONCLUSIONS: This study demonstrates that future headache attacks can be forecasted for a diverse group of individuals over time. Future work will enhance prediction through improvements in the assessment of stress as well as the development of other candidate domains to use in the models.