The prevalence of headache in the adult population of Morocco: a cross-sectional population-based study.

BACKGROUND: The series of population-based studies conducted by the Global Campaign against Headache has, so far, included Pakistan and Saudi Arabia from the Eastern Mediterranean Region. The Maghreb countries of North Africa, also part of this Region, are geographically apart and culturally very different from these countries. Here we report a study in Morocco. METHODS: We applied the standardised methodology of Global Campaign studies, with cluster-randomized sampling in regions of Morocco selected to be representative of its diversities. In three of these regions, in accordance with this methodology, we made unannounced visits to randomly selected households and, from each, interviewed one randomly selected adult member (aged 18-65 years) using the HARDSHIP structured questionnaire translated into Moroccan Arabic and French. In a fourth region (Fès), because permission for such sampling was not given by the administrative authority, people were randomly stopped in streets and markets and, when willing, interviewed using the same questionnaire. This was a major protocol violation. RESULTS: We included 3,474 participants, 1,074 (41.7%) from Agadir, 1,079 (41.9%) from Marrakech, 422 (16.4%) from Tétouan and 899 from Fès. In a second protocol violation, interviewers failed to record the non-participating proportion. In the main analysis, excluding Fès, observed 1-year prevalence of any headache was 80.1% among females, 68.2% among males. Observed 1-day prevalence (headache yesterday) was 17.8%. After adjustment for age and gender, migraine prevalence was 30.8% (higher among females [aOR = 1.6]) and TTH prevalence 32.1% (lower among females [aOR = 0.8]). Headache on ≥ 15 days/month (H15+) was very common (10.5%), and in more than half of cases (5.9%) associated with acute medication overuse (on ≥ 15 days/month) and accordingly diagnosed as probable medication-overuse headache (pMOH). Both pMOH (aOR = 2.6) and other H15+ (aOR = 1.9) were more common among females. In the Fès sample, adjusted prevalences were similar, numerically but not significantly higher except for other H15+. CONCLUSIONS: While the 1-year prevalence of headache among adults in Morocco is similar to that of many other countries, migraine on the evidence here is at the upper end of the global range, but not outside it. H15 + and pMOH are very prevalent, contributing to the high one-day prevalence of headache.

The prevalence and demographic associations of headache in the adult population of Peru: a national cross-sectional population-based study.

BACKGROUND: The Global Campaign against Headache is conducting a series of population-based studies to fill the large geographical gaps in knowledge of headache prevalence and attributable burden. One major region not until now included is South America. Here we present a study from Peru, a country of 32.4 million inhabitants located at the west coast of South America, notable for its high Andes mountains. METHODS: The study was conducted in accordance with the standardized methodology used by the Global Campaign. It was a cross-sectional survey using cluster randomised sampling in five regions to derive a nationally representative sample, visiting households unannounced, and interviewing one randomly selected adult member (aged 18-65 years) of each using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire translated into South American Spanish. The neutral screening question ("Have you had headache in the last year?") was followed by diagnostic questions based on ICHD-3 and demographic enquiry. RESULTS: The study included 2,149 participants from 2,385 eligible households (participating proportion 90.1%): 1,065 males and 1,084 females, mean age 42.0 ± 13.7 years. The observed 1-year prevalence of all headache was 64.6% [95% CI: 62.5-66.6], with age-, gender- and habitation-adjusted prevalences of 22.8% [21.0-24.6] for migraine (definite + probable), 38.9% [36.8-41.0] for tension-type headache (TTH: also definite + probable), 1.2% [0.8-1.8] for probable medication-overuse headache (pMOH) and 2.7% [2.1-3.5] for other headache on ≥ 15 days/month (H15+). One-day prevalence of headache (reported headache yesterday) was 12.1%. Migraine was almost twice as prevalent among females (28.2%) as males (16.4%; aOR = 2.1; p < 0.001), and strongly associated with living at very high altitude (aOR = 2.5 for > 3,500 versus < 350 m). CONCLUSION: The Global Campaign's first population-based study in South America found headache disorders to be common in Peru, with prevalence estimates for both migraine and TTH substantially exceeding global estimates. H15 + was also common, but with fewer than one third of cases diagnosed as pMOH. The association between migraine and altitude was confirmed, and found to be strengthened at very high altitude. This association demands further study.

Posttraumatic Headache.

OBJECTIVE: This article provides an overview of the epidemiology, diagnosis, clinical presentation, pathophysiology, prognosis, and treatment of posttraumatic headache attributed to mild traumatic brain injury (mTBI). LATEST DEVELOPMENTS: The International Classification of Headache Disorders, Third Edition requires that posttraumatic headache begin within 7 days of the inciting trauma. Although posttraumatic headache characteristics and associated symptoms vary, most commonly there is substantial overlap with symptoms of migraine or tension-type headache. New insights into posttraumatic headache pathophysiology suggest roles for neuroinflammation, altered pain processing and modulation, and changes in brain structure and function. Although the majority of posttraumatic headache resolves during the acute phase, about one-third of individuals have posttraumatic headache that persists for at least several months. Additional work is needed to identify predictors and early markers of posttraumatic headache persistence, but several potential predictors have been identified such as having migraine prior to the mTBI, the total number of TBIs ever experienced, and the severity of initial symptoms following the mTBI. Few data are available regarding posttraumatic headache treatment; studies investigating different treatments and the optimal timing for initiating posttraumatic headache treatment are needed. ESSENTIAL POINTS: Posttraumatic headache begins within 7 days of the causative injury. The characteristics of posttraumatic headache most commonly resemble those of migraine or tension-type headache. Posttraumatic headache persists for 3 months or longer in about one-third of individuals. Additional studies investigating posttraumatic headache treatment are needed.

The burden attributable to primary headache disorders in children and adolescents in Ethiopia: estimates from a national schools-based study.

BACKGROUND: We previously reported high prevalences of headache disorders among children (6-11 years) and adolescents (12-17 years) in Ethiopia. Here we provide data on headache-attributed burden collected contemporaneously from the same study participants. Part of the global schools-based programme within the Global Campaign against Headache, the study is the first to present such data from sub-Saharan Africa. METHODS: A cross-sectional survey following the generic protocol for the global study was conducted in six schools (urban and rural), in Addis Ababa city and three regions of Ethiopia. The child or adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaires were self-completed under supervision by pupils in class. Headache diagnostic questions were based on ICHD-3 beta but for the inclusion of undifferentiated headache (UdH). RESULTS: Of 2,349 eligible participants, 2,344 completed the questionnaires (1,011 children [43.1%], 1,333 adolescents [56.9%]; 1,157 males [49.4%], 1,187 females [50.6%]; participating proportion 99.8%). Gender- and age-adjusted 1-year prevalence of headache, reported previously, was 72.8% (migraine: 38.6%; tension-type headache [TTH]: 19.9%; UdH: 12.3%; headache on ≥ 15 days/month (H15+): 1.2%). Mean headache frequency was 2.6 days/4 weeks but, with mean duration of 2.7 h, mean proportion of time with headache was only 1.0% (migraine: 1.4%; TTH: 0.7%; H15+: 9.1%). Mean intensity was 1.8 on a scale of 1-3. Symptomatic medication was consumed on about one third of headache days across headache types. Lost school time reportedly averaged 0.7 days over the preceding 4 weeks, representing 3.5% of school time, but was 2.4 days/4 weeks (12.0%) in the important small minority with H15+. However, actual absences with headache the day before indicated averages overall of 9.7% of school time lost, and 13.3% among those with migraine. Emotional impact and quality-of-life scores reflected other measures of burden, with clear adverse impact gradients (H15 + > migraine > TTH > UdH). CONCLUSIONS: The high prevalence of headache among children and adolescents in Ethiopia, who represent half its population, is associated with substantial burden. Lost school time is probably the most important consequence. Estimates suggest a quite deleterious effect, likely to be reflected in both individual prospects and the prosperity of society.

Migraine treatment: quo vadis? Real-world data study (2015-2022) in Spain.

BACKGROUND: Migraine is a leading cause of disability, estimated to affect one-in-ten people in Spain. This study aimed to describe the management of migraine in Spain and identify improvement areas. METHODS: Non-interventional, retrospective, cross-sectional cohort study conducted using an electronic medical records database covering visits to public healthcare providers for 3% of the Spanish population. Patients with a migraine diagnosis (ICD-9 346) between 01/2015 and 04/2022 were included, as well as their demographic and clinical characteristics, prescribed migraine treatments and the specialty of the prescribing physicians. RESULTS: The database included 61,204 patients diagnosed with migraine. A migraine treatment had been prescribed to 50.6% of patients over the last 24 months (only acute to 69.5%, both acute and preventive to 24.2%, and only preventive to 6.3%). The most frequently prescribed treatments were NSAIDs (56.3%), triptans (44.1%) and analgesics (28.9%). Antidepressants were the most common preventive treatment (prescribed to 17.9% of all treated patients and 58.7% of those treated with a preventive medication), and anti-CGRP monoclonal antibodies the least prescribed (1.7%; 5.7%). In 13.4% of cases, preventive medications were the first treatment: alone in 5.8% of cases and together with an acute medication in 7.6%. A fifth of patients who were initially prescribed with only acute treatment were later prescribed a preventive medication (20.7%). On average, it took 29.4 months for this change to occur. Two-thirds of patients started their preventive treatment in primary care (64.2%). The percentage of patients treated by a neurologist increased with the number of received preventive medications. However, 28.8% of patients who had already been prescribed five or more distinct preventive treatments were not treated by a neurologist. Migraine patients had between 1.2- and 2.2-times higher prevalence of comorbidities than the general population, age-gender adjusted. CONCLUSIONS: Our study emphasizes the need for improved management of migraine in Spain to reduce the risk of chronification and improve patient outcomes. More training and coordination across healthcare professionals is necessary to recognize and address risk factors for migraine progression, including multiple associated comorbidities and several lines of treatment, and to provide personalized treatment plans that address the complex nature of the condition.

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OBJECTIVES: Migraine and tremor share some genetic mutation sites, and clinical studies have also confirmed their correlation. This study aims to explore the clinical and electrophysiological characteristics of migraine patients with concomitant tremor, and to analyze the relevant influential factors of tremor occurrence. METHODS: We retrospectively analyzed the clinical data of 217 migraine patients who visited the Third Affiliated Hospital of Qiqihar Medical University from June 2022 to October 2023. The Clinical Rating Scale for Tremor (CRST), Numerical Rating Scale (NRS), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) were respectively used to assess the tremor symptoms, degree of headache, anxiety, and depression of patients. All patients underwent routine head MR scanning and electromyography examination, and were divided into a migraine with tremor group and a migraine without tremor group based on the electromyogram examination. RESULTS: The migraine with tremor group and the migraine without tremor group were included 52 patients (23.96%) and 165 patients (76.04%), respectively. Compared with the migraine without tremor group, the migraine with tremor group had a longer course and duration of headache, higher frequency of headache attacks, higher NRS score, GAD-7 score, and PHQ-9 score, and fewer weekly physical exercises. The differences were statistically significant (all P<0.05). There were no statistically significant differences in the presence or absence of prodromal headache and white matter hyperintensities (WMHs) between the 2 groups (both P>0.05). The evaluation results of the CRST showed that out of 217 migraine patients, 39 patients (17.97%) were accompanied by tremors. The electromyographic results showed that all 52 migraine patients with tremors had upper limb tremors, including 28 migraine patients with postural tremors and 24 migraine patients with static tremors. Compared with the migraine patients with static tremors, the migraine patients with postural tremors had lower average frequency, peak frequency, and headache onset frequency (all P<0.05). Multiple linear regression analysis showed that frequency of physical exercise, duration of illness, frequency of headache attacks, NRS score, GAD-7 score, and PHQ-9 score were risk factors for migraine patients with concomitant tremors (all P<0.05). CONCLUSIONS: Patients with migraine mainly experience upper limb postural tremors. Reduced physical exercise, long course of disease, long duration of headache, frequent headache attacks, severe headache, anxiety, and depression are risk factors for migraine patients with concomitant tremors.

The prevalence and demographic associations of headache in the adult population of Benin: a cross-sectional population-based study.

BACKGROUND: The Global Burden of Disease (GBD) study is increasingly well informed with regard to headache disorders, but sub-Saharan Africa (SSA) remains one of the large regions of the world with limited data directly derived from population-based studies. The Global Campaign against Headache has conducted three studies in this region: Ethiopia in the east, Zambia in the south and Cameroon in Central SSA. Here we report a similar study in Benin, the first from West SSA. METHODS: We used the same methods and questionnaire, applying cluster-randomized sampling in three regions of the country, randomly selecting households in each region, visiting these unannounced and randomly selecting one adult member (aged 18-65 years) of each household. The HARDSHIP structured questionnaire, translated into Central African French, was administered face-to-face by trained interviewers. Demographic enquiry was followed by diagnostic questions based on ICHD-3 criteria. RESULTS: From 2,550 households with eligible members, we recruited 2,400 participants (participating proportion 94.1%). Headache ever was reported by almost all (95.2%), this being the lifetime prevalence. Headache in the last year was reported by 74.9%. Age-, gender- and habitation-adjusted estimates of 1-year prevalence were 72.9% for all headache, 21.2% for migraine (including definite and probable), 43.1% for TTH (also including definite and probable), 4.5% for probable medication-overuse (pMOH) and 3.1% for other headache on ≥ 15 days/month. One-day (point) prevalence of headache was 14.8% according to reported headache on the day preceding interview. CONCLUSIONS: Overall, these findings are evidence that headache disorders are very common in Benin, a low-income country. The prevalence of pMOH, well above the estimated global mean of 1-2%, is evidence that poverty is not a bar to medication overuse. The findings are very much the same as those in a similar study in its near neighbour, Cameroon. With regard to migraine, they are reasonably in accord with two of three earlier studies in selected Beninese populations, which did not take account of probable migraine. This study adds to the hitherto limited knowledge of headache in SSA.

Association between migraine and the risk of vascular dementia: A nationwide longitudinal study in South Korea.

OBJECTIVE: We aimed to examine the potential association between migraine and vascular dementia (VaD) using a nationwide population database. BACKGROUND: Migraine and VaD showed similar structural and functional changes in pathophysiology process and shared common risk factors, However, whether migraine prevalence increases VaD incidence remains controversial. METHODS: This retrospective population-based cohort study used the medical records from the Korean National Health Insurance System database. Migraine (G43) was defined by using the Tenth Revision of the International Classification of Diseases code. More than two migraine diagnoses at least 3 months apart were defined as "chronic migraine". Cox proportional hazards model estimated hazard ratios (HRs) of VaD for group comparisons. RESULTS: We included 212,836 patients with migraine and 5,863,348 individuals without migraine. During 10 years of follow-up, 3,914 (1.8%) and 60,258 (1.0%) patients with and without migraine, respectively, were newly diagnosed with VaD. After adjustment, patients with migraine showed a 1.21-fold higher risk of VaD than those without migraine (HR = 1.21; 95% confidence interval (CI): 1.17-1.25). Patients with chronic migraine showed a higher cumulative incidence of VaD than those with episodic migraine. The adjusted HR for the VaD incidence with migraine was higher in: (1) patients aged <65 years; (2) women; (3) patients without hypertension, diabetes, or atrial fibrillation; and (4) non-smokers. CONCLUSION: Migraine is associated with an increased risk of VaD, particularly in chronic migraine patients. Incidence of VaD in the setting of migraine may have distinct pathophysiology from that of VaD with traditional cardiovascular risks.

Genetic causal relationship between immune diseases and migraine: a Mendelian randomization study.

Background: Migraine has an increased prevalence in several immune disorders, but genetic cause-effect relationships remain unclear. Mendelian randomization (MR) was used in this study to explore whether immune diseases are causally associated with migraine and its subtypes. Methods: We conducted a two-sample bidirectional multivariate Mendelian randomization study. Single-nucleotide polymorphisms (SNP) for six immune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), allergic rhinitis (AR), asthma and psoriasis, were used as genetic instrumental variables. Summary statistics for migraine were obtained from 3 databases: the International Headache Genetics Consortium (IHGC), UK Biobank, and FinnGen study. MR analyses were performed per outcome database for each exposure and subsequently meta-analyzed. Reverse MR analysis was performed to determine whether migraine were risk factors for immune diseases. In addition, we conducted a genetic correlation to identify shared genetic variants for these two associations. Results: No significant causal relationship was found between immune diseases and migraine and its subtypes. These results were robust with a series of sensitivity analyses. Using the linkage disequilibrium score regression method (LDSC), we detected no genetic correlation between migraine and immune diseases. Conclusion: The evidence from our study does not support a causal relationship between immune diseases and migraine. The mechanisms underlying the frequent comorbidity of migraine and several immune diseases need to be further elucidated.

Unsatisfactory response to acute medications does not affect the medication overuse headache development in pediatric chronic migraine.

BACKGROUND: Chronic migraine (CM) negatively impacts the quality of life of 2 to 4% of pediatric patients. In adults, CM is frequently linked to medication overuse headache (MOH), but there is a much lower prevalence of MOH in children. A suboptimal response to acute therapies may lead to their reduced use, thus preventing MOH development in children and adolescents. The frequency of patients with CM who do not respond to acute therapies was examined in the present study. We investigated whether the prevalence of MOH was different between responders and non-responders. We also examined whether patients receiving prophylactic therapy had an improved response to acute therapy. Finally, we investigated if there was a difference in the frequency of psychiatric comorbidities between responders and non-responders. METHODS: We retrospectively analysed clinical data of all chronic pediatric migraineurs under the age of 18 referred to the Headache Centre at Bambino Gesù Children Hospital in June 2021 and February 2023. ICHD3 criteria were used to diagnose CM and MOH. We collected demographic data, including the age at onset of migraine and the age of the CM course. At baseline and after 3 months of preventive treatment, we evaluated the response to acute medications. Neuropsychiatric comorbidities were referred by the children's parents during the first attendance evaluation. RESULTS: Seventy patients with CM were assessed during the chosen period. Paracetamol was tried by 41 patients (58.5%), NSAIDs by 56 patients (80.0%), and triptans by 1 patient (1.4%). Fifty-one participants (73%) were non-responder to the abortive treatment. The presence of MOH was detected in 27.1% of the whole populations. Regarding our primary aim, MOH was diagnosed in 29% of non-responder patients and 22% of responders (p > 0.05). All patients received preventative treatment. After 3 months of preventive pharmacological therapy, 65.4% of patients who did not respond to acute medications achieved a response, while 34.6% of patients who were non-responder remain non-responder (p < 0.05). Prophylactic therapy was also effective in 69% of patients who responded to acute medication (p < 0.05). Psychiatric comorbidities were detected in 68.6% of patients, with no difference between responders and non-responders (72.2% vs. 67.3%; p = 0.05). CONCLUSIONS: Despite the high prevalence of unresponsiveness to acute therapies in pediatric CM, it does not act as a protective factor for MOH. Moreover, responsiveness to acute drugs is improved by pharmacological preventive treatment and it is not affected by concomitant psychiatric comorbidities.

Healthcare resource utilization and associated costs among patients with migraine in Finland: A retrospective register-based study.

Migraine is a common chronic brain disorder, characterized by recurring and often disabling attacks of severe headache, with additional symptoms such as photophobia, phonophobia and nausea. Migraine affects especially the working age population. The objective of this retrospective observational register-based study was to analyze the use of healthcare services and associated costs in Finnish migraine patients. Study was based on aggregate data from January 1st, 2020, to December 31st, 2021, from the Finnish Institute for Health and Welfare's national registries. Patients were grouped into nine patient groups according to medication prescriptions and diagnoses. Healthcare resource utilization in specialty, primary, and occupational healthcare was assessed and analyzed separately for all-cause and migraine related healthcare contacts from a one-year period. The total number of patients was 175 711, and most (45%) of the patients belonged to a group that had used only one triptan. Migraine related total healthcare resource utilization was greater for patients that had used two or more triptans compared to those that had used only one. The patients with three or more preventive medications had the highest total migraine related healthcare resource utilization of the studied patient cohorts. Of the total annual healthcare costs 11.5% (50.6 million €) was associated to be migraine related costs. Total per patient per year healthcare costs were highest with patients that had used three or more preventive medications (5 626 €) and lowest in those with only one triptan (2 257 €). Our findings are in line with the recent European Headache Federation consensus statement regarding the unmet need in patients who have had inadequate response to two or more triptans. When assessing the patient access and cost-effectiveness of novel treatments for the treatment of migraine within different healthcare systems, a holistic analysis of the current disease burden along with potential gains for patients and healthcare service providers are essential information in guiding decision-making.

Coffee consumption and migraine: a population-based study.

Although coffee is one of the most consumed caffeinated beverages worldwide, the role of coffee consumption in migraine is controversial. This study examined the relationship between coffee consumption and clinical characteristics in participants with migraine compared to those with non-migraine headache. This cross-sectional study used data from a nationwide survey on headache and sleep. Coffee consumption was classified as no-to-low (< 1 cup/day), moderate (1-2 cups/day), or high (≥ 3 cups/day). Of the 3030 survey participants, 170 (5.6%) and 1,768 (58.3%) were identified as having migraine and non-migraine headache, respectively. Coffee consumption tended to increase in the order of non-headache, non-migraine headache, and migraine (linear-by-linear association, p = 0.011). Although psychiatric comorbidities (depression for migraine and anxiety for non-migraine headache) and stress significantly differed according to coffee consumption, most headache characteristics and accompanying symptoms did not differ among the three groups for participants with migraine and non-migraine headache. Response to acute headache treatment-adjusted for age, sex, depression, anxiety, stress, preventive medication use, and current smoking-was not significantly different by coffee consumption in participants with migraine and non-migraine headache. In conclusion, most headache-related characteristics and acute treatment response did not significantly differ by coffee consumption in migraine and non-migraine headache.

Migraine Prevalence, Environmental Risk, and Comorbidities in Men and Women Veterans.

Importance: Migraine is a prevalent and debilitating condition that substantially impacts quality of life. Investigating migraine prevalence, associated comorbidities, and potential military service exposures in veterans, focusing on gender differences, is crucial for targeted interventions and management strategies. Objective: To determine the prevalence of migraine, associated health comorbidities, and potential military service and environmental exposures among men and women US veterans using a large-scale epidemiological sample from the Million Veteran Program (MVP). Design, Setting, and Participants: This cross-sectional study analyzed self-report survey data from the MVP, a large epidemiological sample of US veterans that was started in 2011 and has ongoing enrollment. Eligible participants were selected from the MVP database in 2023. The study included 491 604 veterans to examine migraine prevalence, health comorbidities, demographic characteristics, military service history, and environmental exposures. Data were analyzed from December 2022 to July 2023. Exposures: Military service and environmental factors, such as chemical or biological warfare exposure, were considered. Main Outcomes and Measures: The primary outcome was migraine prevalence among men and women veterans, assessed through self-reported diagnoses. Secondary outcomes included the association between migraine and health comorbidities, demographic characteristics, military service history, and environmental exposures. Results: Of the 491 604 veterans included in this study, 450 625 (91.8%) were men and 40 979 (8.2%) were women. The lifetime prevalence of migraine was significantly higher in women (12 324 of 40 979 [30.1%]) than in men (36 816 of 450 625 [8.2%]). Migraine prevalence varied by race and ethnicity, with the highest prevalence in Hispanic or Latinx women (1213 of 3495 [34.7%]). Veterans with migraine reported worse general health, higher levels of pain, increased pain interference with work, a higher likelihood of psychiatric and neurological health conditions, and greater lifetime opioid use. Specific aspects of military service, including service post-September 2001 and deployment in Operation Enduring Freedom and Operation Iraqi Freedom, and environmental factors, including Agent Orange, chemical and biological welfare, and antinerve agent pills history, were significantly associated with migraine prevalence. Conclusions and Relevance: In this cross-sectional study of migraine, the results highlighted gender differences in migraine prevalence and associated health comorbidities among US veterans. The findings emphasized the need for interdisciplinary approaches to migraine management, increased awareness and education efforts, and population-based screening strategies, particularly for women and Hispanic veterans who are at greater risk. Our findings encourage further research into tailored interventions for specific subpopulations and the impact of military service and environmental exposures on migraine and related health conditions.

Proposing a framework to quantify the potential impact of pharmacokinetic drug-drug interactions caused by a new drug candidate by using real world data about the target patient population.

Drug development teams must evaluate the risk/benefit profile of new drug candidates that perpetrate drug-drug interactions (DDIs). Real-world data (RWD) can inform this decision. The purpose of this study was to develop a predicted impact score for DDIs perpetrated by three hypothetical drug candidates via CYP3A, CYP2D6, or CYP2C9 in type 2 diabetes mellitus (T2DM), obesity, or migraine. Optum Market Clarity was analyzed to estimate use of CYP3A, CYP2D6, or CYP2C9 substrates classified in the University of Washington Drug Interaction Database as moderate sensitive, sensitive, narrow therapeutic index, or QT prolongation. Scoring was based on prevalence of exposure to victim substrates and characteristics (age, polypharmacy, duration of exposure, and number of prescribers) of those exposed. The study population of 14,163,271 adults included 1,579,054 with T2DM, 3,117,753 with obesity, and 410,436 with migraine. For T2DM, 71.3% used CYP3A substrates, 44.3% used CYP2D6 substrates, and 44.3% used CYP2C9 substrates. For obesity, 57.1% used CYP3A substrates, 34.6% used CYP2D6 substrates, and 31.0% used CYP2C9 substrates. For migraine, 64.1% used CYP3A substrates, 44.0% used CYP2D6 substrates, and 28.9% used CYP2C9 substrates. In our analyses, the predicted DDI impact scores were highest for DDIs involving CYP3A, followed by CYP2D6, and CYP2C9 substrates, and highest for T2DM, followed by migraine, and obesity. Insights from RWD can be used to estimate a predicted DDI impact score for pharmacokinetic DDIs perpetrated by new drug candidates currently in development. This score can inform the risk/benefit profile of new drug candidates in a target patient population.

Primary headache disorders among people living with HIV in Lusaka, Zambia.

OBJECTIVE: We completed a cross-sectional survey study to determine headache prevalence and its association with HIV characteristics among people living with HIV (PLHIV) in Lusaka, Zambia. BACKGROUND: Headaches are common but their association with HIV status is unknown. METHODS: The HARDSHIP survey, a headache epidemiology questionnaire previously validated in Zambia, was distributed during a 3-month period to 3666 consecutive adult PLHIV attending routine clinic appointments at the Adult Infectious Diseases Centre at the University Teaching Hospital in Lusaka, Zambia. HIV disease characteristics were abstracted from their charts. RESULTS: 1015 (27.7%) participants responded to the survey. Adjusted for age, 64% reported having a headache within the last year unrelated to another illness. Among participants, 201 met criteria for migraine (20%), 259 for tension-type headache (26%), 18 for probable medication-overuse headache (2%), and 121 for undetermined headache (12%). Prevalence for tension-type headache was significantly higher than that of migraine (P < 0.001). After adjusting for age and sex, higher CD4 counts were associated with migraine. No other associations were observed between overall headache or headache type with HIV disease characteristics including CD4 count, viral load, antiretroviral regimen, and time since HIV diagnosis. CONCLUSIONS: Headaches are highly prevalent among this cohort of PLHIV in Zambia. Optimizing headache treatment and integrating it into routine HIV care may improve quality of life for a substantial proportion of PLHIV in Zambia.

Societal and economic burden of migraine in Spain: results from the 2020 National Health and Wellness Survey.

BACKGROUND: The burden of migraine goes beyond the pain and associated symptoms. We aimed to describe the impact of migraine in healthcare resource utilization (HCRU), work productivity, and mood disorders, as well as its economic cost. METHODS: Case-control study nested in a cross-sectional analysis of patient-reported data collected between 30/12/2019 and 20/04/2020 as part of the National Health and Wellness Survey, from respondents located in Spain. Adults (≥ 18 years old) who reported a physician diagnosis of migraine and ≥ 1 monthly headache days (MHD) in the previous 30 days were included. HCRU, health-related quality-of-life, depression scores, work and activity impairment, and the associated direct and indirect costs were assessed for four cohorts of migraine patients, according to the frequency of headache (MHD: 1-3, 4-7, 8-14, ≥ 15) and compared to a no-migraine control, matched to migraine cases by a propensity score based on demographic and clinical variables. RESULTS: The survey was completed by 595 people with active migraine, of whom 461 (77.4%) experienced < 8 MHDs and 134 (22.6%) ≥ 8 MHDs, and 1,190 non-migraine matched controls. Migraine patients presented worse mental and physical health functioning (SF-12 MCS: 41.9 vs. 44.7, p < 0.001; SF-12 PCS: 48.6 vs. 51.5, p < 0.001), worse self-reported health (EQ-5D VAS: 65.8 vs. 73.5, p < 0.001), more severe depression (PHQ-9: 8.9 vs. 6.1, p < 0.001), and higher overall work impairment (WPAI: 41.4 vs. 25.5, p < 0.001). People with migraine had higher HCRU, twice higher hospitalization rates (17.0% vs. 8.3%, p < 0.001) and 1.6 higher emergency room (ER) visit rates (51.4% vs. 31.2%, p < 0.001). Having migraine translated into higher annual costs with HCRU (€894 vs. €530) and productivity losses (€8,000 vs. €4,780) per person. Respondents with more MHDs presented worse outcomes and higher costs but suffering from 1-3 MHD also increased costs by 51.3%. CONCLUSIONS: Having migraine not only causes a massive impact on patients' quality of life and ability to work, but it also generates considerable economic costs for society. In Spain, having migraine was associated to 1.7 higher costs per patient. The clinical and economic burden increases with the frequency of headaches but is higher than controls even in patients suffering from 1-3 MHD.

Headache in the adult population of Cameroon: prevalence estimates and demographic associations from a cross-sectional nationwide population-based study.

BACKGROUND: Knowledge of headache prevalence, and the burdens attributable to headache disorders, remains incomplete in sub-Saharan Africa (SSA): reliable studies have been conducted only in Zambia (southern SSA) and Ethiopia (eastern SSA). As part of the Global Campaign against Headache, we investigated the prevalence of headache in Cameroon, in Central SSA. METHODS: We used the same methodology as the studies in Zambia and Ethiopia, employing cluster-randomized sampling in four regions of Cameroon, selected to reflect the country's geographic, ethnic and cultural diversities. We visited, unannounced, randomly selected households in each region, and randomly selected one adult member (aged 18-65 years) of each. Trained interviewers administered the Headache-Attributed Restriction, Disability and Impaired Participation (HARDSHIP) structured questionnaire, developed by an international expert consensus group and translated into Central African French. Demographic enquiry was followed by diagnostic questions based on ICHD-3 criteria. RESULTS: Headache was a near-universal experience in Cameroon (lifetime prevalence: 94.8%). Observed 1-year prevalence of headache was 77.1%. Age- and gender-adjusted estimates were 76.4% (95% confidence interval: 74.9-77.9) for any headache, 17.9% (16.6-19.3) for migraine (definite + probable), 44.4% (42.6-46.2) for tension-type headache (TTH; also definite + probable), 6.5% (5.7-7.4) for probable medication-overuse headache (pMOH) and 6.6% (5.8-7.6) for other headache on ≥ 15 days/month (H15 +). One-day prevalence ("headache yesterday") was 15.3%. Gender differentials were as expected (more migraine and pMOH among females, and rather more TTH among males). pMOH increased in prevalence until age 55 years, then declined somewhat. Migraine and TTH were both associated with urban dwelling, pMOH, in contrast, with rural dwelling. CONCLUSIONS: Headache disorders are prevalent in Cameroon. As in Zambia and Ethiopia, estimates for both migraine and TTH exceed global mean estimates. Attributable burden is yet to be reported, but these findings must lead to further research, and measures to develop and implement headache services in Cameroon, with appropriate management and preventative strategies.

Association of mental health symptoms with the migraine-tension-type headache spectrum in the Brazilian longitudinal study of adult health.

OBJECTIVE: To investigate the relationship between mental health symptoms and the migraine-tension-type headache (TTH) spectrum in middle-aged adults from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil study). METHODS: In this cross-sectional analysis (baseline data: 2008-2010), it was evaluated the relationship between each mental health symptom assessed by the Clinical Interview Schedule-Revised (CIS-R) questionnaire and headache subtypes (migraine and TTH) according to international criteria. It was performed binary logistic regression models, with estimated odds ratios (OR) with their respective 95% confidence intervals (CI) adjusted for confounders including migraine attack frequency. RESULTS: Among 13,916 participants, 70.1% reported any major primary headache subtype within the last year. The most common subtype was definite TTH (33.4%), followed by probable migraine (21.0%), definite migraine (8.5%), and probable TTH (7.2%). Our main findings indicated positive associations between anxiety-related symptoms and the migraine-tension type headache (TTH) spectrum with a clear trend toward definite migraine more than tension-type headache. The presence of somatic symptoms presented a high likelihood for the associations with headaches, mainly definite migraine (OR: 7.9, 95% CI: 6.4-9.8), probable migraine (OR: 4.5, 95% CI 3.7-5.4) and probable TTH (OR: 3.0, 95% CI: 2.3-3.8). Other symptoms associated with headache disorders included fatigue, panic, irritability, anxiety symptoms, concentration problems, forgetfulness, depressive symptoms, and worry. The effect of associations remained significant after controlling for headache attack frequency. CONCLUSION: This study provides evidence of consistent associations between mental health symptoms and primary headache disorders, with a higher burden of anxiety-based symptoms observed in people with migraine than those with TTH.

Shared comorbidity of depression, migraine, insomnia, and fibromyalgia in a population-based sample.

BACKGROUND: Depression, migraine, insomnia, and fibromyalgia are reportedly comorbidities. Nevertheless, no study has evaluated the comorbidity of all four of these disorders. This study aimed to investigate the comorbidity of these four disorders. METHODS: Cross-sectional analyses were performed using data of the Circannual Change in Headache and Sleep study, an online nationwide population-based survey. Validated questionnaires were used to diagnose the disorders and measure quality of life. The change of clinical characteristics by addition of any comorbidity was analyzed using the Jonckheere-Terpstra trend test. RESULTS: The prevalence rates of depression, migraine, insomnia, and fibromyalgia were 7.2 %, 5.6 %, 13.3 %, and 5.8 %, respectively. Among the 3030 included participants, 494 (16.3 %), 164 (5.4 %), 40 (1.3 %), and 6 (0.2 %) had one, two, three, and four of these conditions, respectively. The number of headache days per 30 days (Jonckheere-Terpstra trend test, p = 0.011) and migraine-related disability (migraine disability assessment score, p = 0.021) increased with an increase in the number of comorbidities but not with the intensity of headache (visual analog scale, p = 0.225) among participants with migraine. The severity of insomnia (Insomnia Severity Index, p < 0.001) and fibromyalgia (fibromyalgia severity score, p = 0.002) increased with additional comorbidities; however, depression (Patient Health Questionnaire-9, p = 0.384) did not show such an increase. LIMITATIONS: The diagnoses of conditions were based on self-reported questionnaires. CONCLUSIONS: The findings confirmed significant comorbidity between depression, migraine, insomnia, and fibromyalgia. Health professionals should be aware of the probable comorbidity of depression, migraine, insomnia, and fibromyalgia when caring for individuals with any of these four disorders.

The burden of headache disorders in North India: methodology, and validation of a Hindi version of the HARDSHIP questionnaire, for a community-based survey in Delhi and national capital territory region.

BACKGROUND: Knowledge of the prevalence and attributable burden of headache disorders in India is sparse, with only two recent population-based studies from South and East India. These produced conflicting results. A study in North India is needed. We report the methodology of such a study using, and validating, a Hindi translation of the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) questionnaire developed by Lifting The Burden (LTB). Almost half of the Indian population speak Hindi or one of its dialects. METHODS: The study adopted LTB's standardized protocol for population-based studies in a cross-sectional survey using multistage random sampling conducted in urban Delhi and a surrounding rural area. Trained interviewers visited households unannounced, randomly selected one adult member from each and applied the Hindi version of HARDSHIP in face-to-face interviews. The most bothersome headache reported by participants was classified algorithmically into headache on ≥ 15 days/month (H15 +), migraine (including definite and probable) or tension-type headache (including definite and probable). These diagnoses were mutually exclusive. All participants diagnosed with H15 + and a 10% subsample of all others were additionally assessed by headache specialists and classified as above. We estimated the sensitivity and specificity of HARDSHIP diagnoses by comparison with the specialists' diagnoses. RESULTS: From 3,040 eligible households, 2,066 participants were interviewed. The participating proportions were 98.3% in rural areas but 52.9% in urban Delhi. In the validation subsample of 291 participants (149 rural, 142 urban), 61 did not report any headache (seven of those assessed by HARDSHIP, eight by headache specialists and 46 by both) [kappa = 0.83; 95% CI: 0.74-0.91]. In the remaining 230 participants who reported headache in the preceding year, sensitivity, specificity and kappa with (95% CI) were 0.73 (0.65-0.79), 0.80 (0.67-0.90) and 0.43 (0.34-0.58) for migraine; 0.71 (0.56-0.83), 0.80 (0.730.85) and 0.43 (0.37-0.62) for TTH and 0.75 (0.47-0.94), 0.93 (0.89-0.96) and 0.46 (0.34-0.58) for H15 + respectively. CONCLUSION: This study validates the Hindi version of HARDSHIP, finding its performance similar to those of other versions. It can be used to conduct population surveys in other Hindi-speaking regions of India.