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Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Background Caffeine plays a dual role in headache disorders, acting as an analgesic adjuvant while potentially contributing to headache chronification. Its relationship with medication-overuse headache (MOH) and the severity of analgesic dependence remains insufficiently characterized. The study aimed to compare MOH and non-MOH patients in terms of headache burden, psychological characteristics, and caffeine use, and secondarily to assess whether caffeine use disorder is associated with severity of dependence on analgesics in MOH. Methods This is a cross-sectional study conducted on adults with primary headache disorders. Participants were asked to complete the following validated questionnaires: caffeine food frequency (C-FFQ), caffeine use disorder (CUDQ), headache impact test-6 (HIT-6), Severity of Dependence Scale (SDS). Depression Anxiety Stress Scales–12 (DASS-12), and Substance Use Risk Profile Scale (SURPS). Headache diaries were reviewed to document monthly headache days (MHD) and acute medication days (AMD); subsequently, patients were divided into MOH or non-MOH groups, according to ICHD-3 criteria. Results Among 482 patients with primary headache disorders, 160 (33.2%) fulfilled ICHD-3 criteria for MOH. Patients with MOH had significantly higher MHD, AMD, HIT-6 scores, DASS-12 and SURPS total scores than those with non-MOH (all p < 0.001). Heavy caffeine consumption was more prevalent in MOH patients (23.8% vs. 9.3%), who also demonstrated higher CUDQ scores (median 10 vs. 7, p < 0.001). CUDQ scores correlated positively with MHD, AMD, HIT-6, DASS-12, and SURPS (all p < 0.001). Among patients with MOH, SDS scores correlated with MHD, AMD, HIT-6, DASS-12, SURPS, and CUDQ scores (all p < 0.05). Multivariable regression analysis revealed that AMD, HIT-6 score, and CUDQ score were independently associated with SDS scores ( p -value = 0.002, 0.046, 0.002, respectively). Conclusion Patients with MOH had significantly greater headache burden, psychological distress, and caffeine consumption compared with those without MOH. Caffeine use disorder is significantly associated with greater severity of analgesic dependence in patients with MOH. These findings highlight the importance of assessing caffeine-related behaviors when evaluating patients with MOH and suggest that caffeine use disorder may represent a clinically relevant behavioral factor associated with medication dependence severity.

Background Despite consistent epidemiological evidence identifying smoking as a risk factor for medication-overuse headache (MOH), the mechanisms underlying this association remain incompletely elucidated. The aim of this work was to explore the relationship between the severity of analgesic dependence, headache-related disability, nicotine dependence, psychological distress, and addiction-related personality traits in patients with MOH. Methods This multicenter cross-sectional study was conducted on 442 patients with primary headache disorders. Participants underwent structured face-to-face interviews and were asked to fill out the following questionnaires: Headache Impact Test–6 (HIT-6), Severity of Dependence Scale (SDS), Depression Anxiety Stress Scales-12 (DASS-12), and Substance Use Risk Profile Scale (SURPS). Smoking status was documented for all participants. Current smokers were asked to complete Fagerström Test for Nicotine Dependence questionnaire (FTND). Results This study included 442 patients with primary headache disorders, of whom 150 had MOH and 292 did not. Patients with MOH (n = 150) reported significantly higher monthly headache days (MHD), acute medication days (AMD), HIT-6, DASS-12, and SURPS scores than those without MOH (n = 292) (all P-values < 0.001). Smoking prevalence and FTND scores were significantly higher among MOH patients than those without MOH (all P-values < 0.001). Smokers demonstrated higher MHD, AMD, prevalence of MOH, DASS-12, and SURPS scores than non-smokers (all P-values < 0.05). Among smokers, FTND correlated positively with MHD, AMD, HIT-6, DASS-12, and SURPS (all P-values < 0.001). In patients with MOH, SDS scores showed positive correlations with AMD, HIT-6, DASS-12, and SURPS (all P-values < 0.05). Conclusion Severity of dependence on analgesics in patients with MOH is strongly associated with headache burden, nicotine dependence, psychological distress, and addiction-related personality traits.

Background There is growing evidence suggesting a bidirectional relationship between fibromyalgia and migraine. The aim of this work was to study the impact of fibromyalgia on the frequency and severity of migraine headache attacks and the psychological burden in patients with comorbid migraine and fibromyalgia. Methods This cross-sectional comparative study was conducted on 114 patients with comorbid migraine and fibromyalgia and 270 patients with migraine only. All included patients were subjected to a comprehensive assessment of headache through face-to-face interview and assessment of the psychological state using the Depression, Anxiety and Stress Scale-12 (DASS-12). Patients with fibromyalgia were requested to answer the Revised Fibromyalgia Impact Questionnaire (FIQR). Results Patients with comorbid migraine and fibromyalgia had significantly higher monthly migraine days (MMD), headache impact test-6 (HIT-6), and DASS-12 total scores than patients with migraine only ( p -value &lt; 0.001, 0.009, and &lt; 0.001, respectively). There was a statistically significant positive correlation between the FIQR total score and DASS-12 total score ( p -values = 0.001). Additionally, statistically significant positive correlations were found between the FIQR total score and both the MMD and HIT-6 total scores ( p -values = 0.002 and 0.008, respectively). There were also statistically significant positive correlations between the DASS-12 total score and both the MMD and HIT-6 total scores ( p -values = 0.006, 0.027, respectively). Conclusion Fibromyalgia is an aggravating comorbid condition with migraine that is associated with a higher frequency and severity of migraine headache attacks, in addition to increasing the psychological burden.

Background High-quality research studies on therapeutic approaches for migraine management in pediatrics are scarce. Therefore, we conducted a systematic review of current clinical practice guidelines for the diagnosis and management of migraine in children and adolescents to identify areas of consensus and disagreement, as well as critical gaps, paving the way for future updates and improvements. Methods We searched PubMed, WOS, and SCOPUS for guidelines published in the English language in the last 10 years focused on the diagnosis and management of migraine in children and adolescents. Results Following a systematic search, eight eligible guidelines were identified. These guidelines were authored by the American Academy of Neurology (AAN), the European Headache Federation/European Academy of Neurology (EHF/EAN), the International Headache Society (IHS), National Institute for Health and Care Excellence (NICE), the Danish Headache Society, and the German Migraine and Headache Society and the German Society of Neurology. There was a broad consensus on considering the International Classification of Headache Disorders-3rd edition as the diagnostic reference. As regards management, paracetamol and ibuprofen were considered first line in the acute management of migraine, with sumatriptan and zolmitriptan nasal sprays rated as second line. Injectable medications for acute management were overlooked in most guidelines. On the other hand, targeted age groups, dosing, and preventive treatment choices showed areas of variability. Various non-pharmacological measures gained attention in all guidelines. Notably, CGRP antagonists and non-invasive neuromodulation techniques were identified as major gaps. Conclusion The current systematic review highlights areas of agreement and disagreement between existing guidelines on the management of childhood and adolescent migraine and emphasizes the current gaps and opportunities, thus offering a solid foundation for future studies and guidelines.

We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the GRADE approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.

We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the Grading of Recommendations, Assessment, Development and Evaluation approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.

Background In an effort to improve migraine management around the world, the International Headache Society (IHS) has here developed a list of practical recommendations for the acute pharmacological treatment of migraine. The recommendations are categorized into optimal and essential, in order to provide treatment options for all possible settings, including those with limited access to migraine medications. Methods An IHS steering committee developed a list of clinical questions based on practical issues in the management of migraine. A selected group of international senior and junior headache experts developed the recommendations, following expert consensus and the review of available national and international headache guidelines and guidance documents. Following the initial search, a bibliography of twenty-one national and international guidelines was created and reviewed by the working group. Results A total of seventeen questions addressing different aspects of acute migraine treatment have been outlined. For each of them we provide an optimal recommendation, to be used whenever possible, and an essential recommendation to be used when the optimal level cannot be attained. Conclusion Adoption of these international recommendations will improve the quality of acute migraine treatment around the world, even where pharmacological options remain limited.