Combining patient reported outcomes and EHR data to understand population level treatment needs: correcting for selection bias in the migraine signature study

Background Electronic health records (EHR) data can be used to understand population level quality of care especially when supplemented with patient reported data. However, survey non-response can result in biased population estimates. As a case study, we demonstrate that EHR and survey data can be combined to estimate primary care population prescription treatment status for migraine stratified by migraine disability, without and with adjustment for survey non-response bias. We selected disability as it is associated with survey participation and patterns of prescribing for migraine. Methods A stratified random sample of Sutter Health adult primary care (PC) patients completed a digital survey about headache, migraine, and migraine related disability. The survey data from respondents with migraine were combined with their EHR data to estimate the proportion who had prescription orders for acute or preventive migraine treatments. Separate proportions were also estimated for those with mild disability (denoted “mild migraine”) versus moderate to severe disability (denoted mod-severe migraine) without and with correction, using the inverse propensity weighting method, for non-response bias. We hypothesized that correction for non-response bias would result in smaller differences in proportions who had a treatment order by migraine disability status. Results The response rate among 28,268 patients was 8.2%. Among survey respondents, 37.2% had an acute treatment order and 16.8% had a preventive treatment order. The response bias corrected proportions were 26.2% and 11.6%, respectively, and these estimates did not differ from the total source population estimates (i.e., 26.4% for acute treatments, 12.0% for preventive treatments), validating the correction method. Acute treatment orders proportions were 32.3% for mild migraine versus 37.3% for mod-severe migraine and preventive treatment order proportions were 12.0% for mild migraine and 17.7% for mod-severe migraine. The response bias corrected proportions for acute treatments were 24.8% for mild migraine and 26.6% for mod-severe migraine and the proportions for preventive treatment were 8.1% for mild migraine and 12.0% for mod-severe migraine. Conclusions In this study, we combined survey data with EHR data to better understand treatment needs among patients diagnosed with migraine. Migraine-related disability is directly related to preventive treatment orders but less so for acute treatments. Estimates of treatment status by self-reported disability status were substantially over-estimated among those with moderate to severe migraine-related disability without correction for non-response bias.

Type and severity of migraine determines long-term risk of atrial fibrillation in women: a nationwide population-based study

Background Migraine, especially when accompanied by aura, increases the risk of ischemic stroke and has also shown a close relationship with the occurrence of atrial fibrillation (AF). Although the risk of stroke and cardiovascular diseases is higher in women with migraine than in men, there is a lack of evidence for gender differences in the risk of AF in migraineurs. Purpose We sought to evaluate the gender-specific risk of AF according to the type and severity of migraine. Methods The study population included all national health checkup examinees (2009) without a history of AF from the Korean National Health Insurance Service data. The diagnosis and type or severity of migraine were determined using claims data, including diagnostic, procedural, and medication prescription codes. Newly developed non-valvular AF was identified during 10 years of follow-up. Gender-difference in the effect of migraine on AF occurrence was evaluated according to the type and severity of migraine. A multivariate Cox regression model was used to adjust for baseline differences between comparison groups, including age, smoking status, drinking habit, regular physical activity, income level, diabetes mellitus, hypertension, dyslipidemia, body mass index, and glomerular filtration rate as covariates. Results Of a total of 4,020,488 subjects (men, n=2,213,147, women, n=1,807,341) enrolled, 4,986 had migraine with aura (mean age 50.6±14.0, men 29.3%) and 105,029 without aura (mean age 51.6±14.3, men 30.9%). The proportion of migraine with aura among migraine patients was 4% in both gender groups. In the total population, migraine or migraine with aura did not significantly increase the risk of AF. The risk of AF did not increase in a mild degree of migraine, irrespective of gender or the presence of aura. Severe migraine without aura modestly increased the risk of AF in both men and women compared to the control group. (Men, incidence rate [IR] 4.51 per 1,000 person-year, adjusted hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.12–1.31; Female, IR 3.00 per 1,000 person-year, adjusted HR 1.16, 95% CI 1.09–1.22) The increase of AF risk was the most prominent in women who had severe migraine with aura (IR 3.39 per 1,000 person-year, adjusted HR 1.48, 95% CI 1.18–1.85). In contrast, no significant association was observed between AF and migraine with aura in men. (IR 2.28, adjusted HR 0.63, 95% CI 0.39–1.01; P for interaction 0.011) Conclusions Mild migraine was not associated with an increase in AF risk regardless of gender or the presence of aura. Severe migraine without aura showed a mild increase in AF risk without gender-difference, while severe migraine with aura significantly increased the risk of AF only in women, not in men. Surveillance for incident AF and prompt stroke prevention would be beneficial, particularly for young-aged women suffering from severe migraine with aura. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

Efficacy of Topiramate as Prophylactic Treatment of Severe Migraine in Children attending OPD of a Tertiary Care Hospital in Bangladesh- a Randomized Control Trial

Background: Migraine is the most common cause of severe recurrent headache in children. Flunarizine (FNZ) is safe and effective drug for prevention of migraine in children. Topiramate (TPM) is also successful as a preventive drug for migraine in children on randomized, double-blind, placebo-controlled trials. Objective: This study was done to observe the efficacy of Topiramate and also perform a comparison TPM and FNZ in patients with migraine of severe intensity in our situation. Materials & Methods: This was a randomized controlled trial done from January to July, 2018. This study was carried out in the OPD of Paediatric Neurology department, National Institute of Neurosciences, (NINS) Dhaka. Forty Children, 5-15 years old diagnosed as migraine with/without aura with severe intensity were randomized either as in study group (TPM treatment group) and control group (FNZ treatment group). Primary end point of the study was to find out the efficacy and safety of both TPM and FNZ after 4 months of treatment. Result: Post-treatment frequency of headache/month was significantly decreased in both groups (within group, p <0.001). There was no significant difference considering pre and post-treatment frequency of headache/month between two treatment groups. (pre-treatment p- 0.333 and post-treatment p- 0.401). Adverse events were not significantly different between the groups p<0.387. Conclusion: Topiramate is equally efficacious as Flunarizine in prophylactic treatment of severe migraine in children. Bangladesh J Child Health 2020; VOL 44 (3) :153-156

Effect of galcanezumab on severity and symptoms of migraine in phase 3 trials in patients with episodic or chronic migraine

Background Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days compared with placebo. Here, we analyze data from 3 randomized clinical trials (2 episodic trials [EVOLVE-1, EVOLVE-2] and 1 chronic trial [REGAIN]), to examine if galcanezumab also alleviates the severity and symptoms of migraine. Methods The episodic migraine trials were 6-month, double-blind studies in patients with episodic migraine (4–14 monthly migraine headache days). The chronic migraine trial was a 3-month, double-blind study in patients with chronic migraine (≥ 15 headache days per month, where ≥ 8 met criteria for migraine). Patients (18–65 years) were randomized to placebo or galcanezumab 120 mg with a 240-mg loading dose or 240 mg. Patients recorded headache characteristics, duration, severity, and presence of associated symptoms with each headache. The outcomes analyzed were changes from baseline in number of monthly migraine headache days with nausea and/or vomiting, photophobia and phonophobia, aura, and prodromal symptoms other than aura. Additional outcomes analyzed included the number of moderate-to-severe monthly migraine headache days, number of severe migraine headache days, and mean severity of remaining migraine headache days. Change from baseline in the proportion of days with nausea and/or vomiting and the proportion of days with photophobia and phonophobia among the remaining monthly migraine headache days were also analyzed. Results Galcanezumab was superior to placebo in reducing the frequency of migraine headache days with associated symptoms of migraine such as nausea and/or vomiting, photophobia and phonophobia, and prodromal symptoms. Galcanezumab reduced the frequency of migraine headache days with aura in the episodic migraine studies. There was a significant reduction in the proportion of remaining migraine headache days with nausea and/or vomiting for the episodic and chronic migraine studies, and with photophobia and phonophobia for the episodic migraine studies. Galcanezumab was superior to placebo in reducing the number of monthly moderate-to-severe migraine headache days and the overall and monthly severe migraine headache days. Conclusions Galcanezumab reduces the frequency of migraine headache days and can alleviate potentially disabling non-pain symptoms on days when migraine is present in patients with episodic or chronic migraine. Trial registration NCT, NCT02614183 (EVOLVE-1), registered 25 November 2015; NCT, NCT02614196, (EVOLVE-2), registered 25 November 2015; NCT, NCT02614261 (REGAIN), registered 25 November 2015.

Development of a novel zolmitriptan intracutaneous microneedle system (Qtrypta™) for the acute treatment of migraine

M207 is an investigational intracutaneous microneedle therapeutic system for nonoral zolmitriptan delivery. In a Phase I trial, M207 provided faster absorption with a higher 2 h exposure than oral zolmitriptan. In the pivotal trial evaluating efficacy, tolerability and safety in moderate-to-severe migraine attacks, M207 3.8 mg was superior to placebo in providing freedom from headache pain (42 vs 14%) and freedom from most bothersome symptom (68 vs 43%) 2 h post-dose. Treatment-emergent adverse events were mild and transient and most commonly concerned the application site. In post hoc analyses: pain freedom was sustained in approximately 1/3 of patients; efficacy was observed in migraine headaches that are typically more difficult to treat.

Music Medicine as a Component of Acute Migraine Attack Management in The Emergency Room: A Randomized Controlled Open-Label Trial

Background: Acute severe migraine requiring Emergency Room (ER) visit is managed by giving analgesics for pain relief. Since music medicine has been beneficial in other pain syndromes, the study of its effect as a noninvasive add-on to current management is worth pursuing. Objective: To identify if music medicine in addition to medical therapy will reduce the severity and duration of an acute attack of moderate to severe migraine compared to medical management alone. Methods: An open label randomized controlled trial was conducted at the ER of a tertiary hospital in the Philippines from July 2017 to June 2018. Patients who presented at the ER with acute moderate to severe headache fulfilling the ICH-3 criteria for migraine were included. They were randomized to medical therapy or to medical therapy with music medicine. A decrease in the severity of the headache after one hour of medical treatment was the primary outcome. Results: One hundred eighty-three adult migraneurs were included without difference between group in age, gender, and occupation. There was a statistically significant reduction (p=0.037) in pain severity after one hour in 82 of 87 patients given medical treatment with music medicine (94%) compared to 73 of 86 in the medical therapy alone (85%). There were more headache-free patients at one hour in the music group (55% versus 42%, p=0.05). Conclusion: There is decreased duration and severity of pain when music medicine is added to conventional medical therapy in treating patients with an acute migraine. This is the first randomized trial done in the acute ER setting.

Response to Mindfulness-Based Cognitive Therapy Differs Between Chronic and Episodic Migraine

Objective:Evaluate whether the benefits of Mindfulness-Based Cognitive Therapy for Migraine (MBCT-M) on headache disability differs among people with episodic and chronic migraine.Methods:This is a planned secondary analysis of a randomized clinical trial. After a 30-day baseline, participants were stratified by episodic (6-14 days/month) and chronic migraine (15-30 days/month) and randomized to 8 weekly individual sessions of MBCT-M or wait list/treatment as usual (WL/TAU). Primary outcomes [Headache Disability Inventory; Severe Migraine Disability Assessment Scale (scores ≥ 21)] were assessed at Months 0, 1, 2, and 4. Mixed models for repeated measures tested moderation with fixed effects of treatment, time, chronic migraine and all interactions. Planned subgroup analyses evaluated treatment*time in episodic and chronic migraine.Results:Of 60 participants (MBCT-M N = 31, WL/TAU N = 29), 52% had CM. CM moderated the effect of MBCT-M on Severe Migraine Disability Assessment Scale, F(3, 205) = 3.68, p = .013; MBCT-M vs. WL/TAU reduced the proportion of people reporting severe disability to a greater extent among people with EM (-40.0% vs. -14.3%) than CM (-16.4% vs. +8.7%). Subgroup analysis revealed MBCT-M (vs WL/TAU) significantly reduced Headache Disability Inventory for episodic (p = .011) but not chronic migraine (p = .268).Conclusions:MBCT-M is a promising treatment for reducing headache-related disability, with greater benefits in episodic than chronic migraine.Classification of EvidenceThis study provides Class III evidence that MBCT-M reduces headache disability to a greater extent in people with episodic than chronic migraine. NCT02443519.