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Abstract Background We have previously shown headache disorders to be prevalent in in the adult general population of Morocco, especially migraine (30.8%) and headache on ≥ 15 days/month (H15+; 10.5%). This study, collecting data from the same population-based sample, is the first to estimate headache-attributed burden not only in Morocco but, more widely, in the Maghreb countries of North Africa. Methods We used the standard methodology and questionnaire developed by the Global Campaign against Headache. Cluster-based random sampling generated a sample (N = 2,575) representative of the general population aged 18–65 years. Interviews conducted face-to-face enquired into symptom burden (headache frequency, usual duration and usual intensity), and impaired participation in paid work, household work and social or leisure activities during the preceding 3 months. Further enquiry was into headache yesterday (HY). We calculated population-level estimates by factoring in prevalence. Needs assessment estimated the population proportion in need of headache-related health care based on likelihood of benefit. Results Participants with headache of any type spent, on average, 12.5% of their time with headache of intensity rated 2.3 on a scale of 1–3. According to age- and gender-corrected estimates, 7.2–8.4% of all time in the population (calculated by two methods) was spent with headache, H15 + accounting for well over half of this. Impaired participation measured as lost time due to headache averaged 0.5 days from paid work, 1.6 days from household work and 0.3 days from social or leisure activities during the preceding 3 months. Of those with HY (17.8% of the sample), 24.1% of males and 50.9% of females could do nothing or less than half of their planned activity yesterday. At population level this diluted to 7.0% of all activity lost to headache. At least 30% of the population were estimated to need headache-related health care. Conclusion Headache disorders cause much ill health in the adult population of Morocco. While this will be of obvious concern to health policy in Morocco, the call for provision of health care for almost one third of this population is challenging. On the other hand, economic policy should recognise the lost-productivity costs of inadequately treated headache, especially migraine.

Abstract Background We have previously found that almost two thirds (64.6%) of adults in Peru have an active headache disorder. Here, using data from the same sample, we present attributed burden at individual and population levels. We use these data to assess need for headache-related health care among this population. Methods We used the standard methodology of the Global Campaign against Headache. Cluster-sampling from five geographical regions of Peru (Cajamarca, Lima, Piura, Puno, San Martín) generated a sample representative of the population aged 18–65 years. At unannounced visits to households, we interviewed one adult from each using the HARDSHIP questionnaire. We assessed symptom burden in terms of headache frequency and usual duration and intensity, and impaired participation in paid work, household work and social or leisure activities using the HALT index. To assess need for health care, we counted all those with headache on ≥ 15 days/month (H15+), those with migraine on ≥ 3 days/month, and those with migraine or tension-type headache meeting either of two criteria: a) proportion of time in ictal state (pTIS) > 3.3% and intensity ≥ 2 (moderate-to-severe); b) ≥ 3 lost days from paid and/or household work during the preceding 3 months. We derived population-level estimates by factoring in prevalences. Results The sample size was N = 2,149. From individual data, we estimated population-level pTIS at 1.9–2.5%, this proportion of all time among adults in Peru being spent with headache, with migraine the greatest contributor (1.2%). At population level, headache was responsible for 0.5 days lost from paid work and 1.0 days from household work per person per 3 months, with migraine again the biggest contributor (0.2 and 0.5 days). However, at individual level, H15 + was associated with greatest burden (pTIS 14.9–24.9%; 2.3–4.5 lost workdays/3 months). A quarter of the sample (n = 590; 27.5%) fulfilled one or more of our health-care need criteria. Conclusion Headache disorders are responsible for high levels of ill health and economic burden in Peru, with a substantial requirement for health care. Health and economic policies balancing health benefits against the cost of providing care should take account of the productivity losses that might be recovered, and the expected cost-offset.

Abstract Background Having previously shown headache disorders to be prevalent in Mongolia, here we elaborate on headache as a public-health concern in this country, reporting symptom burden and headache-attributed impaired participation at individual and societal levels, and conducting a health-care needs assessment. Methods The study followed the standardized methodology developed by the Global Campaign against Headache, generating a representative general-population sample through multi-level randomized cluster sampling. Participants aged 18–65 years were interviewed at unannounced household visits by interviewers administering the HARDSHIP questionnaire. Symptom burden was established through questions on frequency, duration and intensity of headache, with proportion of time in ictal state calculated from frequency and duration. Individual impaired participation was established through the HALT questionnaire, enquiring into lost time from paid and household work and from leisure activities. Symptom burden and impaired participation yesterday were also assessed in those reporting headache yesterday. Population-level estimates were derived by factoring in prevalence. Results The total sample included 2,043 participants. Those reporting any headache in the last year (n = 1,351) spent, on average, 9.7% of all their time with headache, losing 1.3 workdays and 2.4 household days/3 months. These losses were considerably higher among those with probable medication-overuse headache (37.5%, 3.5 workdays, 6.7 household days) or other headache on ≥ 15 days/month (H15+) (21.9%, 2.4 workdays, 5.1 household days). At population-level (including those with and without headache), 6.2–7.4% of all time was spent with headache, 3.1% with H15+; 0.8 workdays and 1.4 household days/person/3 months were lost to headache, 0.3 workdays and 0.6 household days to migraine (the biggest contributor of all headache types). Our needs assessment estimated that one third (33.2%) of the adult population of Mongolia have headache (mostly migraine or H15+) likely to benefit from health care. Conclusion This first population-based study on headache burden in Mongolia shows high levels of individual and societal burden, with H15 + the cause of greater burden at population level than migraine and TTH combined. Migraine, however, has the biggest impact on the nation’s productivity. From a purely economic perspective, Mongolia, with limited health resources, would probably be best served by focusing on mitigating migraine-attributed burden.

Abstract Background We have previously shown headache to be highly prevalent in Cameroon. Here we present the attributed burden. We also perform a headache-care needs assessment. Methods This was a cross-sectional survey among adults (18–65 years) in the general population. Multistage cluster-sampling in four regions (Centre, Littoral, West and Adamawa), home to almost half the country’s population, generated a representative sample. We used the standardised methodology of the Global Campaign against Headache, including the HARDSHIP questionnaire, with diagnostic questions based on ICHD-3 and enquiries into symptom burden, impaired participation (lost productivity and disengagement from social activity), quality of life (QoL) using WHOQoL-8, and willingness to pay (WTP) for effective care. We defined headache care “need” in terms of likelihood of benefit, counting all those with probable medication-overuse headache (pMOH) or other headache on ≥ 15 days/month (H15 +), with migraine on ≥ 3 days/month, or with migraine or tension-type headache (TTH) and meeting either of two criteria: a) proportion of time in ictal state (pTIS) > 3.3% and intensity ≥ 2 (moderate-to-severe); or b) ≥ 3 lost days from paid and/or household work in the preceding 3 months. Results Among 3,100 participants, mean frequency of any headache was 6.7 days/month, mean duration 13.0 h and mean intensity 2.3 (moderate). Mean pTIS was 9.8%, which (with prevalence factored in) diluted to 6.1–7.4% of all time in the population. Most time was spent with H15 + (5.3% of all time), followed by TTH (1.0%) and migraine (0.8%). For all headache, mean lost days/3 months were 3.4 from paid work, 3.0 from household work and 0.6 from social/leisure activities, diluting to 2.5, 2.2 and 0.6 days/3 months in the population. QoL (no headache: 27.9/40) was adversely impacted by pMOH (25.0) and other H15 + (26.0) but not by migraine (28.0) or TTH (28.0). WTP (maximally XAF 4,462.40 [USD 7.65] per month) was not significantly different between headache types. An estimated 37.0% of adult Cameroonians need headache care. Conclusion Headache disorders in Cameroon are not only prevalent but also associated with high attributed burden, with heavily impaired participation. Headache-care needs are very high, but so are the economic costs of not providing care.

Abstract Background A global schools-based programme within the Global Campaign against Headache is estimating the burden of headache in children (6–11 years) and adolescents (12–17 years), cluster-sampling the world by conducting national studies in all world regions. Its purpose is to complement population-based studies in adults, adding to knowledge of the burden of headache and informing educational and health policies. This study in Benin was the third in the programme from sub-Saharan Africa (SSA). Methods We followed the generic protocol for the global study. In a cross-sectional survey, the child and adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire were administered to pupils within their classes in 16 schools selected from across the country to be representative of its diversities. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of undifferentiated headache (UdH). Results Very large proportions of pupils were absent on the survey days. The sampled population defined by class registers totalled 11,802 pupils, of whom only 2,488 were present. A further 193 pupils (or their parents) declined the survey. The surveyed sampled (N = 2,295; males 1,156 [50.4%], females 1,139 [49.6%]) included 1,081 children (47.1%) and 1,214 adolescents (52.9%), with a non-participating proportion (193/2,488) of 7.8%. Headache ever was reported by 97.3% of the sample. Age- and gender-adjusted 1-year prevalences, according to responses given, were 53.4% for migraine (almost three quarters of this being probable migraine), 21.3% for tension-type headache, 8.2% for UdH, 1.0% for probable medication-overuse headache (pMOH) and 2.6% for other headache on ≥ 15 days/month (H15+). Both pMOH and other H15 + were substantially more prevalent among adolescents. Conclusion The finding for migraine is anomalous, but, within this series of studies, the same was found in Zambia and similar in Ethiopia, both in SSA. While many cases identified as probable migraine, especially among children, might better have been diagnosed as UdH, the true prevalence of migraine almost certainly exceeds 21%. Regardless of diagnosis, headache is very common among children and adolescents in Benin. The study sounds an alarm with regard to pMOH as a developing problem pre-adulthood.

Abstract Background Our recent studies have shown headache disorders to be very common in the central and western sub-Saharan countries of Benin and Cameroon. Here we report headache in nearby Mali, a strife-torn country that differs topographically, culturally, politically and economically. The purposes were to estimate headache-attributed burden and need for headache care. Methods We used cluster-random sampling in seven of Mali’s eleven regions to obtain a nationally representative sample. During unannounced household visits by trained interviewers, one randomly selected adult member (18–65 years) from each household was interviewed using the structured HARDSHIP questionnaire, with enquiries into headache in the last year and, additionally, headache yesterday (HY). Headache on ≥ 15 days/month (H15+) was diagnosed as probable medication-overuse headache (pMOH) when associated with acute medication use on ≥ 15 days/month, and as “other H15+” when not. Episodic headache (on

Abstract Background India is a large and populous country where reliable data on headache disorders are relatively scarce. This study in northern India (Delhi and National Capital Territory Region [NCR], including surrounding districts in the States of Haryana, Uttar Pradesh and Rajasthan) continues the series of population-based studies within the Global Campaign against Headache and follows an earlier study, using the same protocol and questionnaire, in the southern State of Karnataka. Methods This cross-sectional study used the Global Campaign’s established methodology. Biologically unrelated Indian nationals aged 18–65 years were included through multistage random sampling in both urban and rural areas of NCR. Interviews at unannounced household visits followed the structured Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire in its original English version or in the validated Hindi version. Demographic enquiry was followed by a neutral headache screening question and diagnostic questions based on the International Classification of Headache Disorders edition 3 (ICHD-3), which focused on each respondent’s most bothersome headache. Questions about headache yesterday (HY) enabled estimation of 1-day prevalence. A diagnostic algorithm first identified participants reporting headache on ≥ 15 days/month (H15+), diagnosing probable medication-overuse headache (pMOH) in those also reporting acute medication use on ≥ 15 days/month, and “other H15+” in those not. To all others, the algorithm applied ICHD-3 criteria in the order definite migraine, definite tension-type headache (TTH), probable migraine, probable TTH. Definite and probable diagnoses were combined. Results Adjusted for age, gender and habitation, 1-year prevalences were 26.3% for migraine, 34.1% for TTH, 3.0% for pMOH and 4.5% for other H15+. Female preponderance was seen in all headache types except TTH: migraine 35.7% vs. 15.1% (aOR = 3.3; p

Abstract Background We recently found headache disorders to be highly prevalent among children (aged 6–11 years) and adolescents (aged 12–17) in Iran (gender- and age-adjusted 1-year prevalences: migraine 25.2%, tension-type headache 12.7%, undifferentiated headache [UdH] 22.1%, probable medication-overuse headache [pMOH] 1.1%, other headache on ≥ 15 days/month [H15+] 3.0%). Here we report on the headache-attributed burden, taking evidence from the same study. Methods In a cross-sectional survey, following the generic protocol for the global schools-based study led by the Global Campaign against Headache, we administered the child and adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire in 121 schools, purposively selected to reflect the country’s diversities. Pupils self-completed these in class, under supervision. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of UdH (defined as mild headache with usual duration

Abstract Background We have previously shown headache to be highly prevalent among adults in Saudi Arabia. Here we estimate associated symptom burden and impaired participation (impaired use of time, lost productivity and disengagement from social activity), and use these estimates to assess headache-related health-care needs in Saudi Arabia. Methods A randomised cross-sectional survey included 2,316 adults (18–65 years) from all 13 regions of the country. It used the standardised methodology of the Global Campaign against Headache with a culturally mandated modification: engagement by cellphone using random digit-dialling rather than door-to-door visits. Enquiry used the HARDSHIP questionnaire, with diagnostic questions based on ICHD-3 beta, questions on symptom burden, enquiries into impaired participation using the HALT index and questions about activity yesterday in those reporting headache yesterday (HY). Health-care “need” was defined in terms of likelihood of benefit. We counted all those with headache on ≥ 15 days/month, with migraine on ≥ 3 days/month, or with migraine or TTH and meeting either of two criteria: a) proportion of time in ictal state (pTIS) > 3.3% and intensity ≥ 2 (moderate-severe); b) ≥ 3 lost days from paid work and/or household chores during 3 months. Results For all headache, mean frequency was 4.3 days/month, mean duration 8.4 h, mean intensity 2.3 (moderate). Mean pTIS was 3.6%. Mean lost days from work were 3.9, from household chores 6.6, from social/leisure activities 2.0. Of participants reporting HY, 37.3% could do less than half their expected activity, 19.8% could do nothing. At population-level (i.e., for every adult), 2.5 workdays (potentially translating into lost GDP), 3.6 household days and 1.3 social/leisure days were lost to headache. According to HY data, mean total impaired participation (not distinguishing between work, household and social/leisure) was 6.8%. A total of 830 individuals (35.8%) fulfilled one or more of our needs assessment criteria. Conclusion A very high symptom burden is associated with a commensurately high burden of impaired participation. The economic cost appears to be enormous. Over a third of the adult population are revealed to require headache-related health care on the basis of being likely to benefit, demanding highly efficient organization of care.

Abstract 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.

Abstract 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.

Abstract The World Health Organization (WHO) Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders was developed by WHO to address the worldwide challenges and gaps in provision of care and services for people with epilepsy and other neurological disorders and to ensure a comprehensive, coordinated response across sectors to the burden of neurologic diseases and to promote brain health across life-course. Headache disorders constitute the second most burdensome of all neurological diseases after stroke, but the first if young and midlife adults are taken into account. Despite the availability of a range of treatments, disability associated with headache disorders, and with migraine, remains very high. In addition, there are inequalities between high-income and low and middle income countries in access to medical care. In line with several brain health initiatives following the WHOiGAP resolution, herein we tailor the main pillars of the action plan to headache disorders: (1) raising policy prioritization and strengthen governance; (2) providing effective, timely and responsive diagnosis, treatment and care; (3) implementing strategies for promotion and prevention; (4) fostering research and innovation and strengthen information systems. Specific targets for future policy actions are proposed. The Global Action Plan triggered a revolution in neurology, not only by increasing public awareness of brain disorders and brain health but also by boosting the number of neurologists in training, raising research funding and making neurology a public health priority for policy makers. Reducing the burden of headache disorders will not only improve the quality of life and wellbeing of people with headache but also reduce the burden of neurological disorders increasing global brain health and, thus, global population health.

Abstract In order to pursue its purpose of reducing the global burden of headache, the Global Campaign against Headache has gathered data on headache-attributed burden from countries worldwide. These data, from the individual participants in adult population-based studies and child and adolescent schools-based studies, are being collated in two databases, which will be powerful resources for research and teaching and rich information sources for health policy. Here we briefly describe the structure and content of these databases, and announce the intention to make them available in due course as a free good.

Abstract Introduction Worldwide, far from all of those who would benefit make use of headache services, largely because of clinical, social, and political barriers to access. Identifying the factors contributing to low healthcare utilization can generate evidence to guide health policy. Our purpose here is better to characterize healthcare utilization patterns in Denmark. Methods The Headache in Denmark (HINDER) study is a nationwide cross-sectional survey of people with headache, conducted using SurveyXact (Rambøll Group A/S, Copenhagen). Healthcare utilization was assessed in a study sample generated by population screening and recruitment. Data collection occurred over two weeks, from September 23rd until October 4th, 2021. The questions enquired into disease characteristics, management, burden, medication intake and healthcare utilization. Results The number of participants included in the HINDER panel was 4,431, with 2,990 (67.5%: 2,522 [84.3%] female, 468 [15.7%] male; mean age 40.9 ± 11.6 years) completing the survey. One quarter of participants (27.7%) disagreed or strongly disagreed that they were able to manage their headache attacks. Most participants (81.7%) agreed or strongly agreed that their headache was a burden in their everyday lives. The most reported acute medications, by 87.2% of participants, were simple analgesics; of note, 8.6% reported using opioids for their headache. One quarter of participants (24.4%) had never consulted a medical doctor for their headache; one in six (16.5%: more than two thirds of the 24.4%) had never done so despite agreeing or strongly agreeing that their headache was a burden in their everyday lives. Two thirds (65.3%) of participants overall, and almost three quarters (72.4%) of those with weekly headache, had tried one or more complementary or alternative therapies outside conventional medical care. Conclusions Our findings are indicative of inadequate delivery of headache care in a country that provides free and universal coverage for all its residents. The implications are twofold. First, it is not sufficient merely to make services available: public education and increased awareness are necessary to encourage uptake by those who would benefit. Second, educational interventions in both pre- and postgraduate settings are necessary, but a prerequisite for these is a resetting of policy priorities, properly to reflect the very high population ill-health burden of headache.

Abstract Background In an earlier paper, we examined the relationship between headache-attributed disability, measured as proportion of time in ictal state, and lost productivity. In a linear model, we found positive and significant associations with lost paid worktime, lost household worktime and total lost productivity (paid + household), but with high variance, which was increased when headache intensity was introduced as a factor. We speculated that analyses based on headache frequency alone as the independent variable, eliminating both the subjectivity of intensity estimates and the uncertainties of duration, might show stronger associations. Methods Focusing on migraine, we used individual participant data from 16 countries surveyed either in population-based studies or in the Eurolight project. These data included frequency (headache days/month), usual attack duration (hours), usual headache intensity (“not bad”, “quite bad”, “very bad”) and lost productivity from paid and household work according to enquiries using the Headache-Attributed Lost Time (HALT) questionnaire. We used multiple linear regressions, calculating regression equations along with unstandardized and standardized regression coefficients. We made line and bar charts to visualize relationships. Results Both frequency and intensity were significant predictors of lost productivity in all multiple linear regressions, but duration was a non-significant predictor in several of the regressions. Predicted productivity in paid work decreased among males by 0.75–0.85 days/3 months for each increase of 1 headache day/month, and among females by 0.34–0.53 days/3 months. In household chores, decreases in productivity for each added day/month of headache were more similar (0.67–0.87 days/3 months among males, 0.83–0.89 days/3 months among females). Visualizations showed that the impact of duration varied little across the range of 2–24 h. The standardized regression coefficients demonstrated that frequency was a much better predictor of lost productivity than intensity or duration. Conclusion In the relationship between migraine-attributed impairment (symptom burden) and lost productivity, frequency (migraine days/month) is the dominating variable – more important than headache intensity and far more important than episode duration. This has major implications for current practice in headache care and for health policy and health-resource investment. Preventative drugs, grossly underutilized in current practice, offer a high prospect of economic benefit (cost-saving), but new preventative drugs are needed with better efficacy and/or tolerability.

Abstract Background Observational studies on the prevalence of premonitory symptoms in people with migraine, preceding the headache pain (or aura) phase, have shown conflicting results. We conducted a systematic review and meta-analysis to estimate the prevalence, and relative frequency among clinic populations, of premonitory symptoms in people with migraine, overall and of the multifarious individual symptoms, and to review the methodologies used to assess them. Methods We searched PubMed and Embase for studies published from database inception until 31st of May 2022. Two investigators independently screened titles, abstracts, and full texts. We retrieved observational studies that reported the prevalence/relative frequency of one or more premonitory symptoms in people with migraine. Two investigators independently extracted data and assessed risk of bias. Results were pooled using random-effects meta-analysis. Our main outcomes were the percentage of people with migraine who experienced at least one premonitory symptom and the percentages who experienced different individual premonitory symptoms. To describe our outcomes, we used the terms prevalence for data from population-based samples and relative frequency for data from clinic-based samples. We also descriptively and critically assessed the methodologies used to assess these symptoms. Results The pooled estimated prevalence in population-based studies of at least one premonitory symptom was 29% (95% CI: 8–63; I2 99%) and the corresponding pooled estimated relative frequency in clinic-based studies was 66% (95% CI: 45–82; I2 99%). The data from clinic-based studies only supported meta-analysis of 11 of 96 individual symptoms, with relative frequency estimates ranging from 11 to 49%. Risk of bias was determined as high in 20 studies, moderate in seven, and low in two. Conclusions The substantial between-study heterogeneity demands cautious interpretation of our estimates. Studies showed wide methodological variations, and many lacked rigor. Overall, the evidence was insufficient to support reliable prevalence estimation or characterization of premonitory symptoms. More data are needed, of better quality, to confirm the existence of a distinctive premonitory phase of migraine, and its features. Methodological guidelines based on expert consensus are a prerequisite.

Abstract Background The Global Campaign against Headache collects data from children (6–11 years) and adolescents (12–17) to inform health and education policies and contribute to the Global Burden of Disease (GBD) study. This survey in Zambia, part of this global enquiry, was the second from sub-Saharan Africa (SSA). Methods Following the generic protocol, this was a schools-based cross-sectional survey. We used the child and adolescent versions of the structured Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, self-completed by pupils within classes, in a total of nine schools in Lusaka (urban) and Copperbelt (semi-rural). These two of Zambia’s ten provinces were selected to represent the country’s urban/rural divide. Headache diagnostic questions were based on ICHD-3 except for undifferentiated headache (UdH). Results Of 2,759 potential participants, 2,089 (615 children [29.4%], 1,474 adolescents [70.6%]) completed questionnaires (participating proportion 75.7%). Children were therefore under-represented (mean age 13.1 ± 2.8 years), while gender distribution (1,128 [54.0%] male, 961 [46.0%] female) was close to expectation. Observed lifetime prevalence of headache was 97.5%. Gender- and age-adjusted 1-year prevalence estimates were 85.8% for all headache, 53.2% for migraine (definite 17.5%, probable 35.7%), 12.1% for tension-type headache (TTH), 14.8% for UdH, 3.3% for all headache on ≥ 15 days/month and 0.9% for probable medication-overuse headache. Headache durations were short: only 28.6% of participants with any headache, and only 10.5% of those diagnosed as probable migraine, reported usual durations of > 2 h (the threshold for definite migraine). Of the latter, 36.6% reported

Abstract Introduction Large numbers of people with headache who would benefit are not reached by headache services. Among the causes are poor or disorganized provision of headache services, but reluctance to seek healthcare has frequently been identified as a significant barrier. We conducted a national survey of people with headache to assess the extent of this problem in Denmark, a country with well organized, highly resourced, and readily accessible services. Methods We conducted a nationwide cross-sectional survey of adults ≥ 18 years old in Denmark reporting at least one headache day in the last year. We used social media (Facebook) to publicize and drive a recruitment campaign. The survey investigated five items: (1) disease burden, (2) social life, (3) presenteeism, (4) social support, and (5) healthcare utilization. Results We included 6,567 respondents from May 2021 to June 2021; 70.2% were female, 39.8% male, and mean age was 43.2 ± 13.4 years. Of the respondents, 54.2% reported headache at least once a week, 33.4% reported headache a couple of times a month, and 12.4% reported headache a couple of times a year. Two-thirds of respondents (66.6%) reported that headache limited their social lives occasionally or frequently. Most respondents (86.8%) reported going to work or attending educational activities occasionally or more frequently even though they had headache. Half of the respondents (49.5%) experienced lack of understanding of their headaches from people occasionally or more frequently. Almost half of respondents (43.7%) had never consulted a medical doctor for their headache; even of those with weekly headache, more than a quarter (28.3%) had never done so in their lifetimes. Conclusions Headache disorders continue to be a problem, even in a high-income country with free and easily accessible headache services. Further studies are needed to investigate and clarify why even people with the highest burden are hesitant to seek and make use of widely available headache services.

Abstract The Global Campaign against Headache, as a collaborative activity with the World Health Organization (WHO), was formally launched in Copenhagen in March 2004. In the month it turns 18, we review its activities and achievements, from initial determination of its strategic objectives, through partnerships and project management, knowledge acquisition and awareness generation, to evidence-based proposals for change justified by cost-effectiveness analysis.

Abstract Background According to the Global Burden of Disease (GBD) study, headache disorders are among the most prevalent and disabling conditions worldwide. GBD builds on epidemiological studies (published and unpublished) which are notable for wide variations in both their methodologies and their prevalence estimates. Our first aim was to update the documentation of headache epidemiological studies, summarizing global prevalence estimates for all headache, migraine, tension-type headache (TTH) and headache on ≥15 days/month (H15+), comparing these with GBD estimates and exploring time trends and geographical variations. Our second aim was to analyse how methodological factors influenced prevalence estimates. Methods In a narrative review, all prevalence studies published until 2020, excluding those of clinic populations, were identified through a literature search. Prevalence data were extracted, along with those related to methodology, world region and publication year. Bivariate analyses (correlations or comparisons of means) and multiple linear regression (MLR) analyses were performed. Results From 357 publications, the vast majority from high-income countries, the estimated global prevalence of active headache disorder was 52.0% (95%CI 48.9–55.4), of migraine 14.0% (12.9–15.2), of TTH 26.0% (22.7–29.5) and of H15+ 4.6% (3.9–5.5). These estimates were comparable with those of migraine and TTH in GBD2019, the most recent iteration, but higher for headache overall. Each day, 15.8% of the world’s population had headache. MLR analyses explained less than 30% of the variation. Methodological factors contributing to variation, were publication year, sample size, inclusion of probable diagnoses, sub-population sampling (e.g., of health-care personnel), sampling method (random or not), screening question (neutral, or qualified in severity or presumed cause) and scope of enquiry (headache disorders only or multiple other conditions). With these taken into account, migraine prevalence estimates increased over the years, while estimates for all headache types varied between world regions. Conclusion The review confirms GBD in finding that headache disorders remain highly prevalent worldwide, and it identifies methodological factors explaining some of the large variation between study findings. These variations render uncertain both the increase in migraine prevalence estimates over time, and the geographical differences. More and better studies are needed in low- and middle-income countries.

Abstract Background Headache disorders are disabling, with major consequences for productivity, yet the literature is silent on the relationship between headache-attributed disability and lost productivity, often erroneously regarding the two as synonymous. We evaluated the relationship empirically, having earlier found that investment in structured headache services would be cost saving, not merely cost-effective, if reductions in headache-attributed disability led to > 20% pro rata recovery of lost productivity. Methods We used individual participant data from Global Campaign population-based studies conducted in China, Ethiopia, India, Nepal, Pakistan and Russia, and from Eurolight in Lithuania, Luxembourg and Spain. We assessed relationships in migraine and probable medication-overuse headache (pMOH), the most disabling common headache disorders. Available symptom data included headache frequency, usual duration and usual intensity. We used frequency and duration to estimate proportion of time in ictal state (pTIS). Disability, in the sense used by the Global Burden of Disease study, was measured as the product of pTIS and disability weight for the ictal state. Impairment was measured as pTIS * intensity. Lost productivity was measured as lost days (absence or 20% in all countries but Pakistan). Analysing impairment rather than disability increased variability. For pMOH, with smaller numbers, associations were generally weaker, occasionally negative and mostly not significant. Conclusion Relief of disability through effective treatment of migraine is expected, in most countries, to recover > 20% pro rata of lost productivity, above the threshold for investment in structured headache services to be cost saving.

Headache disorders are a common cause of disability globally and lead not only to physical disability but also to financial strain, higher rates of mental health disorders such as depression and anxiety, and reduced economic productivity which negatively impacts gross domestic product (GDP) on a national scale. While data about headache are relatively scarce in low- and middle-income countries (LMICs), those available suggest that headache disorders occur on a similar scale in LMICs as they do in high-income countries. In this manuscript, we discuss common clinical, political, economic and social barriers to headache care for people living in LMICs. These barriers, affecting every aspect of headache care, begin with community perceptions and cultural beliefs about headache, include ineffective headache care delivery systems and poor headache care training for healthcare workers, and extend through fewer available diagnostic and management tools to limited therapeutic options for headache. Finally, we review potential solutions to these barriers, including educational interventions for healthcare workers, the introduction of a tiered system for headache care provision, creation of locally contextualized diagnostic and management algorithms, and implementation of a stepped approach to headache treatment.

Abstract Background Health economic evaluations support health-care decision-making by providing information on the costs and consequences of health interventions. No universally accepted methodology exists for modelling effectiveness and cost-effectiveness of interventions designed to close treatment gaps for headache disorders in countries of Europe (or elsewhere). Our aim here, within the European Brain Council’s Value-of-Treatment project, was to develop headache-type-specific analytical models to be applied to implementation of structured headache services in Europe as the health-care solution to headache. Methods We developed three headache-type-specific decision-analytical models using the WHO-CHOICE framework and adapted these for three European Region country settings (Luxembourg, Russia and Spain), diverse in geographical location, population size, income level and health-care systems and for which we had population-based data. Each model compared current (suboptimal) care vs target care (delivered in accordance with the structured headache services model). Epidemiological and economic data were drawn from studies conducted by the Global Campaign against Headache; data on efficacy of treatments were taken from published randomized controlled trials; assumptions on uptake of treatments, and those made for Healthy Life Year (HLY) calculations and target-care benefits, were agreed with experts. We made annual and 5-year cost estimates from health-care provider (main analyses) and societal (secondary analyses) perspectives (2020 figures, euros). Results The analytical models were successfully developed and applied to each country setting. Headache-related costs (including use of health-care resources and lost productivity) and health outcomes (HLYs) were mapped across populations. The same calculations were repeated for each alternative (current vs target care). Analyses of the differences in costs and health outcomes between alternatives and the incremental cost-effectiveness ratios are presented elsewhere. Conclusions This study presents the first headache-type-specific analytical models to evaluate effectiveness and cost-effectiveness of implementing structured headache services in countries in the European Region. The models are robust, and can assist policy makers in allocating health budgets between interventions to maximize the health of populations.

Abstract Background There have been several calls for estimations of costs and consequences of headache interventions to inform European public-health policies. In a previous paper, in the absence of universally accepted methodology, we developed headache-type-specific analytical models to be applied to implementation of structured headache services in Europe as the health-care solution to headache. Here we apply this methodology and present the findings. Methods Data sources were published evidence and expert opinions, including those from an earlier economic evaluation framework using the WHO-CHOICE model. We used three headache-type-specific analytical models, for migraine, tension-type-headache (TTH) and medication-overuse-headache (MOH). We considered three European Region case studies, from Luxembourg, Russia and Spain to include a range of health-care systems, comparing current (suboptimal) care versus target care (structured services implemented, with provider-training and consumer-education). We made annual and 5-year cost estimates from health-care provider and societal perspectives (2020 figures, euros). We expressed effectiveness as healthy life years (HLYs) gained, and cost-effectiveness as incremental cost-effectiveness-ratios (ICERs; cost to be invested/HLY gained). We applied WHO thresholds for cost-effectiveness. Results The models demonstrated increased effectiveness, and cost-effectiveness (migraine) or cost saving (TTH, MOH) from the provider perspective over one and 5 years and consistently across the health-care systems and settings. From the societal perspective, we found structured headache services would be economically successful, not only delivering increased effectiveness but also cost saving across headache types and over time. The predicted magnitude of cost saving correlated positively with country wage levels. Lost productivity had a major impact on these estimates, but sensitivity analyses showed the intervention remained cost-effective across all models when we assumed that remedying disability would recover only 20% of lost productivity. Conclusions This is the first study to propose a health-care solution for headache, in the form of structured headache services, and evaluate it economically in multiple settings. Despite numerous challenges, we demonstrated that economic evaluation of headache services, in terms of outcomes and costs, is feasible as well as necessary. Furthermore, it is strongly supportive of the proposed intervention, while its framework is general enough to be easily adapted and implemented across Europe.

Abstract In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the “patient journey”) with perplexing obstacles. High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary. The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded. It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.

Abstract Background We recently showed headache to be common in children (aged 7–11 years) and adolescents (aged 12–17) in Lithuania. Here we provide evidence from the same study of the headache-attributable burden. Methods Following the generic protocol for Lifting The Burden’s global schools-based study, this cross-sectional survey administered self-completed structured questionnaires to pupils within classes in 24 nationally representative schools selected from seven regions of the country. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH; defined as mild headache with usual duration

Abstract Background The Global Campaign against Headache collects data from children (7–11 years) and adolescents (12–17 years) both to inform health and education policies and to contribute to the Global Burden of Disease (GBD) study. This survey in Mongolia was part of this global enquiry. Methods Following the generic protocol for the global enquiry, this was a schools-based cross-sectional survey. Self-completed structured questionnaires were administered, within classes, in seven schools in four districts of the Capital city and three rural areas of Mongolia, selected to represent the country’s diversities. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of undifferentiated headache (UdH). Results Of 4515 potential participants, 4266 completed the questionnaire (children 2241 [52.5%], adolescents 2025 [47.5%]; males 2107 [49.4%], females 2159 [50.6%]). Children were therefore slightly over-represented, although overall mean age was 11.3 ± 3.3 years (range: 6–17; median 11). The non-participation proportion was 4.5%. Observed lifetime prevalence of headache was 81.0%. Gender- and age-adjusted 1-year prevalence was 59.4% (migraine: 27.3%; tension-type headache [TTH]: 16.1%; UdH: 6.6%; all headache on ≥15 days/month: 4.2%; probable medication-overuse headache: 0.7%). All headache types except UdH were more prevalent among females than males, and all were more prevalent among adolescents than children, although UdH represented a higher proportion of all headache in children (13.0%) than in adolescents (10.0%). Headache yesterday was reported by 15.9% of the sample, 26.0% of those with headache. Conclusions At least in adolescents, headache in Mongolia is no less common than in adults. The clear difference from similar studies in other countries was a lower prevalence of UdH, perhaps a consequence of reporting bias in a non-troublesome headache (mild and short-lasting by definition). This study informs policy in Mongolia and, with no similar study yet from elsewhere in Western Pacific Region, makes an important contribution to the global enquiry.

Abstract Background The Global Burden of Disease (GBD) study establishes headache as the second-highest cause of disability worldwide. Because most headache data in GBD are from adults, leading to underestimation of headache-attributed burden, a global schools-based programme within the Global Campaign against Headache is contributing data from children (7–11 years) and adolescents (12–17 years). This national study in Ethiopia is the first in this programme reported 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. Structured questionnaires were self-completed under supervision by pupils within their classes. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH). Results Of 2349 potential participants, 2344 completed the questionnaire (1011 children [43.1%], 1333 adolescents [56.9%]; 1157 males [49.4%], 1187 females [50.6%]), a participation proportion of 99.8%. Gender- and age-adjusted 1-year prevalence of headache was 72.8% (migraine: 38.6%; tension-type headache: 19.9%; UdH: 12.3%; all headache on ≥15 days/month: 1.2%; probable medication-overuse headache: 0.2%). Headache was more prevalent in females (76.2%) than males (71.0%), a finding reflected only in migraine among the headache types. Headache was more prevalent among adolescents (77.6%) than children (68.4%), reflected in all types except migraine, although prevalence of UdH fell sharply after age 14 years to 3.9%. For headache overall, findings matched those in Turkey and Austria, obtained with the same questionnaire, but the high prevalence of migraine, not increasing with age, was surprising. The study highlighted diagnostic difficulties in young people, especially when poorly educated, with migraine diagnoses driven by improbably high proportions reporting nausea (44.8%) and vomiting (28.0%) as usual symptoms accompanying their headaches. Conclusions Headache is very common in children and adolescents in Ethiopia. This has major public-health implications, since half the country’s population are aged under 18 years.

Abstract Background While the Global Burden of Disease (GBD) study reports headache disorders as the second-highest cause of disability worldwide, the headache data in GBD come very largely from adults. This national study in Lithuania was part of a global schools-based programme within the Global Campaign against Headache contributing data from children (7–11 years) and adolescents (12–17 years). Methods The methods followed the generic protocol for the global study. The basic study design was a cross-sectional survey. Self-completed structured questionnaires were administered, within classes, in 24 schools selected from seven regions of Lithuania to be nationally representative. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH). Results Of 3714 potential participants, 2505 (children 1382 [55.2%], adolescents 1123 [44.8%]; males 1169 [46.7%], females 1336 [53.3%]) completed the questionnaire. Adolescents and males were therefore relatively under-represented, with non-participation (32.6%) due in most cases to lack of parental consent. Observed lifetime prevalence of headache was 92.2%. Gender- and age-adjusted 1-year prevalence was 76.6% (migraine: 21.4%; tension-type headache [TTH]: 25.6%; UdH: 24.0%; all headache on ≥15 days/month: 3.9%; probable medication-overuse headache: 0.8%). All headache types except UdH were more prevalent among females than males, and among adolescents than children. UdH showed a complex relationship with age, but represented 38.0% of all reported headache in children, 27.4% in adolescents. Headache yesterday (HY) was reported by 17.5%, almost double the 9.8% predicted from prevalence and headache frequency to have headache on any day. The reason was unclear. Conclusions Findings were not very different from those reported in Turkey and Austria, but with more TTH. Headache has, therefore, again been shown to be common in children and adolescents, and UdH confirmed as a headache type that must be recognised and included in accounts of headache in these age groups.

Abstract Background The large geographical gaps in our knowledge of the prevalence and burden of headache disorders include most of Eastern Mediterranean Region (EMR). Following a nationwide population-based study in Pakistan, we present here a similar study from Kingdom of Saudi Arabia (KSA). Both were conducted as projects within the Global Campaign against Headache The two purposes of this study were to inform national health policy and contribute to global knowledge of headache disorders. Methods We surveyed Arabic-speaking adults aged 18–65 years in all 13 regions of KSA. While previous Global Campaign studies have engaged participants by calling at randomly selected households, the culture of KSA made this unacceptable. Participants were, instead, contacted by cell-phone (since cell-phone coverage exceeded 100% in KSA), using random-digit dialling. Trained interviewers used a culturally adapted version of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, with diagnostic enquiry based on ICHD-II. We estimated 1-year prevalences of the headache disorders of public-health importance (migraine, tension-type headache [TTH] and probable medication-overuse headache [pMOH]) and examined their associations with demographic variables. Results A total of 2316 participants (mean age of 32.2 ± 10.7 years; 62.3% male; 37.7% female) were included (participation proportion 86.5%). Gender and age distributions imperfectly matched those of the national population, requiring adjustments for these to prevalence estimates. Observed 1-year prevalence of all headache was 77.2%, reducing to 65.8% when adjusted. For headache types, adjusted 1-year prevalences were migraine 25.0%, TTH 34.1%, pMOH 2.0% and other headache on ≥15 days/month 2.3%. Adjusted 1-day prevalence of any headache was 11.5%. Migraine and pMOH were associated with female gender (ORs: 1.7 and 4.7; p 45 years (OR: 0.4; p = 0.0143) while pMOH was most prevalent in those aged 46–55 years (OR: 2.7; p = 0.0415). TTH reportedly became more common with increasing level of education. Conclusion Prevalences of migraine and TTH in KSA are considerably higher than global averages (which may be underestimated), and not very different from those in Pakistan. There is more pMOH in KSA than in Pakistan, reflecting, probably, its higher-income status and greater urbanisation (facilitating access to medication).

Abstract Background In the ongoing Global Campaign endeavour to improve knowledge and awareness of headache prevalence worldwide, Mongolia is a country of interest. It sits between Russia and China, in which prevalence is, respectively, much higher and much lower than the estimated global mean. We conducted a population-based study in Mongolia both to add to knowledge and to inform local health policy. Methods Using standardized methodology with cluster random sampling, we selected Mongolian adults (aged 18–65 years) from five regions reflecting the country’s diversities. They were interviewed by trained researchers, cold-calling at their homes, using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire following pilot-testing. ICHD-3 beta diagnostic criteria were applied. Results N = 2043 (mean age 38.0 [±13.4] years, 40% urban-dwelling and 60% rural), with a non-participation proportion of 1.7%. Males were somewhat underrepresented, for which corrections were made. The crude 1-year prevalence of any headache was 66.1% (95% CI: 64.0–68.2%), with a strong female preponderance (OR: 2.2; p

Abstract Background Headache disorders are highly prevalent worldwide, but not so well investigated in children and adolescents as in adults: few studies have included representative nationwide samples. No data exist for Austria until now. In a representative sample of children and adolescents in Austria, we estimated the prevalence and attributable burden of headache disorders, including the new diagnostic category of “undifferentiated headache” (UdH) defined as mild headache lasting less than 1 hour. Methods Within the context of a broader national mental health survey, children and adolescents aged 10–18 years were recruited from purposively selected schools. Mediated self-completed questionnaires included sociodemographic enquiry (gender, age, socioeconomic status, family constellation, residence [urban or rural] and migration background). Prevalence and attributable burden of all headache, UdH, migraine (definite plus probable), tension-type headache (TTH: definite plus probable) and headache on ≥15 days/month (H15+) were assessed using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Health-related quality of life (HrQoL) was assessed using the KIDSCREEN questionnaire. Results Of 7643 selected pupils, 3386 (44.3%) completed the questionnaires. The 1-year prevalence of headache was 75.7%, increasing with age and higher in girls (82.1%) than in boys (67.7%; p

Abstract Background Even though migraine and other primary headache disorders are common and debilitating, major health surveys in Brazil have not included them. We repair this omission by combining data on non-communicable diseases (NCDs) in the Brazilian National Health Survey (PNS) 2013 with epidemiological data on migraine prevalence and severity in Brazil. The purpose is to rank migraine and its impact on public healthh among NCDs in order to support public-health policy toward better care for migraine in Brazil. Methods Data from PNS, a cross-sectional population-based study, were merged with estimates made by the Brazilian Headache Epidemiology Study (BHES) of migraine prevalence (numbers of people affected and of candidates for migraine preventative therapy) and migraine-attributed disability. Results Migraine ranked second in prevalence among the NCDs, and as the highest cause of disability among adults in Brazil. Probable migraine accounted for substantial additional disability. An estimated total of 5.5 million people in Brazil (or 9.5 million with probable migraine included) were in need of preventative therapy. Conclusion On this evidence, migraine should be included in the next health surveys in Brazil. Public-health policy should recognize the burden of migraine expressed in public ill health, and promote health services offering better diagnosis and treatment.

Abstract Objectives Using the findings of the Global Burden of Disease Study (GBD), we report the burden of primary headache disorders in the Eastern Mediterranean Region (EMR) from 1990 to 2016. Methods We modelled headache disorders using DisMod-MR 2.1 Bayesian meta-regression tool to ensure consistency between prevalence, incidence, and remission. Years lived with disability (YLDs) were calculated by multiplying prevalence and disability weight (DW) of migraine and tension-type headache (TTH). We assumed primary headache disorders as non-fatal, so their YLD is equal to disability-adjusted life years (DALYs). Results Migraine and TTH were the second and twentieth leading causes of YLDs in EMR. Between 1990 and 2016, the absolute YLD numbers of migraine and TTH increased from 2.3 million (95% uncertainty interval (UI): 1.5–3.2) to 4.7 million (95%UI: 3–6.5) and from 383 thousand (95%UI: 240–562) to 816 thousand (95%UI: 516–1221), respectively. During the same period, age-standardised YLD rates of migraine and TTH in EMR increased by 0.7% and 2.5%, respectively, in comparison to a small decrease in the global rates (0.2% decrease in migraine and TTH). The bulk of burden due to headache occurred in the 30–49 year age group, with a peak at ages 35–44 years. The age-standardised YLD rates of both headache disorders were higher in women with female to male ratio of 1.69 for migraine and 1.38 for TTH. All countries of the EMR except for Somalia and Djibouti had higher age-standardised YLD rates for migraine and TTH in compare to the global rates. Libya and Saudi Arabia had the highest increase in age-standardised YLD rates of migraine and TTH, respectively. Conclusion The findings of this study show that primary headache disorders are a major and a growing cause of disability in EMR. Since 1990, burden of primary headache disorders has constantly been higher in EMR compared to rest of the world, which indicates that health systems in EMR must focus further on developing and implementing preventive and management strategies to control headache.

Abstract Background Headache disorders are an important global public-health problem, but under-diagnosed, undertreated and under-prioritized. Deficiencies in health care for headache, present everywhere, are likely to be greater in poorly-resourced countries. This study reports on health-care utilization for headache in Nepal, a low-income country with high headache burden. Methods We took data from a cross-sectional, nationwide population-based door-to-door survey, with multistage cluster random sampling. Face-to-face structured interviews included enquiry into consultations with professional health-care providers (HCPs), and investigations and treatments for headache. Analysis included associations with sociodemographic variables and indices of symptom severity. Results Of 2100 participants, 1794 reported headache during the preceding year (mean age 36.1 ± 12.6 years; male/female ratio 1:1.6). Of these, 58.4% (95% CI: 56.1–60.7%) had consulted at least once in the year with HCPs at any level, most commonly (25.0%) paramedical; 15.0% had consulted pharmacists, 10.8% general physicians and 7.6% specialists (of any type). Participants with probable medication-overuse headache consulted most (87.0%), followed by those with migraine (67.2%) and those with tension-type headache (48.6%; p

Abstract Background Headache is a leading disabler in adults worldwide. In children and adolescents, the same may be true but the evidence is much poorer. It is notable that published epidemiological studies of these age groups have largely ignored headaches not fulfilling any specific set of ICHD criteria, although such headaches appear to be common. A new approach to these is needed: here we introduce, and investigate, a diagnostic category termed “undifferentiated headache” (UdH), defined in young people as recurrent mild-intensity headache of

Abstract Background Migraine is prevalent everywhere, and disabling. It is also neglected: consequently, it is under-diagnosed and undertreated. We analysed data from the Eurolight study on consultations and utilization of migraine-specific medications as indicators of adequacy of medical care in Europe. Methods Eurolight was a cross-sectional questionnaire-based survey in 10 European countries. Sampling was population-based in six (Germany, Italy, Lithuania, Luxembourg, Netherlands, Spain) and from consecutive patients attending general practitioners (GPs) for any reason in three (Austria, France, UK). Additional samples in Netherlands and Spain, and the only sample from Ireland, were recruited by lay headache organisations. We recorded migraine prevalence and frequency, and utilization of medical services and medications (acute and preventative). Results Among 9247 participants (mean age 43.9 ± 13.9 years, M/F ratio 1:1.4), 3466 (37.6%) were diagnosed with migraine (definite or probable). Of these, 1175 (33.8%) reported frequent migraine (> 5 days/month) and might clearly expect benefit from, and therefore had need of, preventative medication. In population-based samples, minorities of participants with migraine had seen a GP (9.5–18.0%) or specialist (3.1–15.0%), and smaller minorities received adequate treatment: triptans 3.4–11.0%, with Spain outlying at 22.4%; preventative medication (1.6–6.4% of those eligible, with Spain again outlying at 13.7%). Proportions were greater in GP-based samples (13.6–24.5% using triptans, 4.4–9.1% on preventative medication) and among those from lay organisations (46.2–68.2% and 16.0–41.7%). Participants with migraine who had consulted specialists (3.1–33.8%) were receiving the best care by these indicators; those treated by GPs (9.5–29.6%) fared less well, and those dependent on self-medication (48.0–84.2%) were, apparently, inadequately treated. Conclusion In wealthy European countries, too few people with migraine consult physicians, with proportionately too many of these seeing specialists, and migraine-specific medications are used inadequately even among those who do. These findings represent yet another call for action in Europe to improve care for people with headache. Education of both health-care providers and the public should be central to this action.

Abstract Background There are no robust population-based Australian data on prevalence and attributed burden of migraine and medication-overuse headache (MOH) data. In this pilot cross-sectional study, we aimed to capture the participation rate, preferred response method, and acceptability of self-report questionnaires to inform the conduct of a future nationwide migraine/MOH epidemiological study. Methods We developed a self-report questionnaire, available in hard-copy and online, including modules from the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, the Eq. 5D (quality of life), and enquiry into treatment gaps. Study invitations were mailed to 20,000 randomly selected households across Australia’s two most populous states. The household member who most recently had a birthday and was aged ≥ 18 years was invited to participate, and could do so by returning a hard-copy questionnaire via reply-paid mail, or by entering responses directly into an online platform. Results The participation rate was 5.0% (N = 1,000). Participants’ median age was 60 years (IQR 44–71 years), and 64.7% (n = 647) were female. Significantly more responses were received from areas with relatively older populations and middle-level socioeconomic status. Hard copy was the more commonly chosen response method (n = 736). Females and younger respondents were significantly more likely to respond online than via hard-copy. Conclusions This pilot study indicates that alternative methodology is needed to achieve satisfactory engagement in a future nationwide migraine/MOH epidemiological study, for example through inclusion of migraine screening questions in well-resourced, interview-based national health surveys that are conducted regularly by government agencies. Meanwhile, additional future research directions include defining and addressing treatment gaps to improve migraine awareness, and minimise under-diagnosis and under-treatment.

Abstract 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 3,500 versus

Abstract 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.

Abstract 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.

Abstract 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.

Abstract Background Headache disorders are disabling and have a significant impact on productivity. The relationship between these two consequences is of considerable economic and political interest. We enquired into it through a systematic search of the English-language literature. Methods We followed PRISMA guidelines in specifying search terms and syntax and in article selection. We used the term “disability” in the search, accepting any meaning that authors attached to it, but this proved problematic. Accordingly, we adopted the definition used in the Global Burden of Disease study. In article selection, we included only those that purported to measure disability as so defined and lost productivity. We reviewed the full texts of those selected. We included further articles identified from review of the bibliographies of selected articles. Results The literature search found 598 studies, of which 21 warranted further review. Their bibliographies identified another four of possible relevance. On full-text reading of these 25, all were rejected. Ten applied incompatible definitions of disability and/or lost productivity. Two did not measure both. Four reported lost productivity but not disability. Eight studies reported and measured both but did not assess the association between them or provide the means of doing so. One was purely methodological. Conclusions The literature is silent on the relationship between headache-attributed disability and lost productivity. In view of its health economic and political importance, empirical studies are required to remedy this. A prerequisite is to clarify what is meant by “disability” in this context.

Abstract Background The first manuscript in this series delineated a model of structured headache services, potentially cost-effective but requiring formal cost-effectiveness analysis (CEA). We envisaged a need for a new outcome measure for this purpose, applicable to all forms of treatment, care and care-delivery systems as opposed to comparisons of single-modality treatments. Conception and delineation A literature review confirmed the lack of any suitable established measure. We prioritised construct validity, simplicity, comprehensiveness and expression in intuitive units. We noted that pain was the key burdensome symptom of migraine and episodic tension-type headache (TTH), that pain above a certain level was disabling, that it was difficult to put economic value to pain but relatively easy to do this for time, a casualty of headache leading to lost productivity. Alleviation of pain to a non-disabling level would be expected to bring restoration of function. We therefore based the measure on time spent in the ictal state (TIS) of migraine or TTH, either as total TIS or proportion of all time. We expressed impact on health, in units of time, as TIS*DW, where DW was the disability weight for the ictal state supplied by the Global Burden of Disease (GBD) studies. If the time unit was hours, TIS*DW yielded hours lived with (or lost to) disability (HLDs), in analogy with GBD’s years lived with disability (YLDs). Utility assessment Acute treatments would reduce TIS by shortening attack duration, preventative treatments by reducing attack frequency; health-care systems such as structured headache services would have these effects by delivering these treatments. These benefits were all measurable as HLDs-averted. Population-level estimates would be derived by factoring in prevalence, but also taking treatment coverage and adherence into account. For health-care systems, additional gains from provider-training (promoting adherence to guidelines and, therefore, enhancing coverage) and consumer-education (improving adherence to care plans), increasing numbers within populations gaining the benefits of treatments, would be measurable by the same metric. Conclusions The new outcome measure expressed in intuitive units of time is applicable to treatments of all modalities and to system-level interventions for multiple headache types, with utility for CEA and for informing health policy.

Abstract With support from Lifting The Burden , a UK-registered charitable organization, a nationwide survey of headache disorders in the Chinese adult population was conducted in 2008–2009. This project, which was within the Global Campaign against Headache, showed that headache disorders have a major adverse impact on public health in China. Subsequently, as essential support for implementing headache services around the country, an enactment of stage 3 (intervention) of the Global Campaign against Headache − the continuing medical education (CME) program Headache Schools − was established. ‘SMART’ (Screen, Migraine, Aura, Red flag and Treatment), a systematic and operational disease management model, was introduced with the aims of enhancing neurologists’ knowledge of migraine, standardizing their diagnostic and treatment approaches, and improving their practices and outcomes. To date, 615 neurologists have been trained and 135 headache clinics have been established. In future, as we promote SMART in CME, we can use the database of our computerized clinical decision support systems to evaluate the impact on treatment outcomes.

Abstract Background Headache disorders are the third-highest cause of disability worldwide, with migraine and medication-overuse headache (MOH) the major contributors. In Ethiopia we have shown these disorders to be highly prevalent: migraine 17.7%, TTH 20.6%, probable MOH (pMOH) 0.7%, any headache yesterday (HY) 6.4%. To inform local health policy, we now estimate disability and other burdens attributable to headache in this country. Methods In a cross-sectional survey using cluster-randomized sampling, we visited households unannounced in four diverse regions (urban and rural) of Ethiopia. We interviewed one member (18–65 years old) of each household using the HARDSHIP structured questionnaire. Screening and diagnostic questions based on ICHD-II were followed by burden enquiry in multiple domains. We estimated disability using disability weights (DWs) from the Global Burden of Disease 2013 study. Results We interviewed 2385 participants (1064 [44.7%] male, 596 [25.0%] urban; participating proportion 99.8%). Reported mean intensity of migraine was 2.6 (scale 1–3). People with migraine spent 11.7% of their time in the ictal state (DW: 0.441); they were therefore 5.2% disabled overall. Pain and disability from TTH were much lower. Mean intensity of pMOH was 2.95. People with pMOH spent 60.2% of time with headache (DW: 0.223), and were 13.4% disabled. Average proportions of per-person lost productive time were, for migraine, 4.5% from paid work, 5.3% from household work; for pMOH they were 29.2% and 16.0%. There were highly-disabled minorities, and large gender differences, males losing more paid workdays, females more household workdays. All headache types were associated with impairments in quality of life. Across the population aged 18–65 years (effectively the working population), disability from headache was 1.4%, with 1.6% of workdays lost (half from migraine). Estimates from HY, eliminating recall error, were highly compatible. Conclusions Ethiopia is a low-income country, and cannot afford these losses – including, perhaps, 1.6% of GDP. Political action is necessary, aimed at mitigating both the economic burden and the associated ill health. WHO has recommended structured headache services with their basis in primary care as the most efficient, effective, affordable and equitable solution, potentially cost-saving. We believe they can be implemented within Ethiopia’s existing health-care infrastructure.

Abstract Background The Eurolight project assessed the impact of headache disorders in ten EU countries, using the same structured questionnaire but varying sampling methods. In Lithuania, sample selection employed methods in line with consensus recommendations for population-based burden-of-headache studies. Methods The survey was cross-sectional. We identified, from the Residents’ Register Service, a sample of inhabitants of Kaunas city and surrounding Kaunas region reflecting age (in the range 18–65 years), gender and rural/urban distributions of Lithuania. Medical students called unannounced at their homes and conducted face-to-face interviews employing a structured questionnaire. Results Of 1137 people in the pre-identified sample, 573 (male 237 [41.4%], female 336 [58.6%]; mean age 40.9 ± 13.8 years) completed interviews (participation proportion: 50.4%). Gender-adjusted 1-year prevalences were: any headache 74.7%; migraine 18.8%; tension-type headache (TTH) 42.2%; all headache on ≥15 days/month 8.6%; probable medication-overuse headache (pMOH) 3.2%. Migraine (OR: 3.6) and pMOH (OR: 2.9) were associated with female gender. All headache types except TTH were associated with significantly diminished quality of life. Migraine caused a mean 4.5% loss in paid worktime per affected male and 3.5% per affected female. Lost per-person times due to TTH were much less, but to pMOH and other headache on ≥15 days/month much higher. Among the entire workforce, lost productivity to migraine was estimated at 0.7%, to TTH 0.3% and to pMOH or other headache on ≥15 days/month 0.5%. The total of 1.5% may translate directly into lost GDP. Alternative calculations based on headache yesterday (with little recall error) produced, for all headache, a corroborating 1.7%. Similar losses from household work would also drain the nation’s economy. Our findings were comparable to those from earlier studies using similar methods in Russia and Georgia. Conclusions The multiple burdens from headache in Lithuania indicate substantial ill-health and unmet need for health care. The heavy burdens on individuals are matched by heavy economic burden. Of particular concern is the high prevalence of headache on ≥15 days/month, seen also in Russia and Georgia. Health policy in Lithuania must heed WHO’s advice that effective treatment of headache, clearly desirable for its health benefits, is also expected to be cost-saving.

Summary: Background: The Nordic countries have commonalities in gender equality, economy, welfare, and health care, but differ in culture and lifestyle, which might create country-wise health differences. This study compared life expectancy, disease burden, and risk factors in the Nordic region. Methods: Life expectancy in years and age-standardised rates of overall, cause-specific, and risk factor-specific estimates of disability-adjusted life-years (DALYs) were analysed in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Data were extracted for Denmark, Finland, Iceland, Norway, and Sweden (ie, the Nordic countries), and Greenland, an autonomous area of Denmark. Estimates were compared with global, high-income region, and Nordic regional estimates, including Greenland. Findings: All Nordic countries exceeded the global life expectancy; in 2017, the highest life expectancy was in Iceland among females (85·9 years [95% uncertainty interval [UI] 85·5–86·4] vs 75·6 years [75·3–75·9] globally) and Sweden among males (80·8 years [80·2–81·4] vs 70·5 years [70·1–70·8] globally). Females (82·7 years [81·9–83·4]) and males (78·8 years [78·1–79·5]) in Denmark and males in Finland (78·6 years [77·8–79·2]) had lower life expectancy than in the other Nordic countries. The lowest life expectancy in the Nordic region was in Greenland (females 77·2 years [76·2–78·0], males 70·8 years [70·3–71·4]). Overall disease burden was lower in the Nordic countries than globally, with the lowest age-standardised DALY rates among Swedish males (18 555·7 DALYs [95% UI 15 968·6–21 426·8] per 100 000 population vs 35 834·3 DALYs [33 218·2–38 740·7] globally) and Icelandic females (16 074·1 DALYs [13 216·4–19 240·8] vs 29 934·6 DALYs [26 981·9–33 211·2] globally). Greenland had substantially higher DALY rates (26 666·6 DALYs [23 478·4–30 218·8] among females, 33 101·3 DALYs [30 182·3–36 218·6] among males) than the Nordic countries. Country variation was primarily due to differences in causes that largely contributed to DALYs through mortality, such as ischaemic heart disease. These causes dominated male disease burden, whereas non-fatal causes such as low back pain were important for female disease burden. Smoking and metabolic risk factors were high-ranking risk factors across all countries. DALYs attributable to alcohol use and smoking were particularly high among the Danes, as was alcohol use among Finnish males. Interpretation: Risk factor differences might drive differences in life expectancy and disease burden that merit attention also in high-income settings such as the Nordic countries. Special attention should be given to the high disease burden in Greenland. Funding: Bill & Melinda Gates Foundation. The work on this paper was supported by the Research Council of Norway through FRIPRO (project number 262030) and by the Norwegian Institute of Public Health.