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Objective: To describe treatment patterns and direct healthcare costs over 3 years following initiation of standard of care acute and preventive migraine medications in patients with migraine in the United States. Background: There are limited data on long‐term (>1 year) migraine treatments patterns and associated outcomes. Methods: This was a retrospective, observational cohort study using US claims data from the IBM® MarketScan® Research Database (January 2010–December 2017). Adults were included if they had a prescription claim for acute migraine treatments (AMT) or preventive migraine treatments (PMT) in the index period (January 2011–December 2014). The AMT cohort was categorized as persistent, cycled, or added‐on subgroups; the PMT cohort was categorized PMT‐persistent, switched without gaps, or cycled with gaps. Migraine‐specific annual direct costs (2017 US$) across AMT and PMT cohort subgroups were summarized at baseline through 3 years from index (follow‐up). Results: During the index period, 20,778 and 42,259 patients initiated an AMT and a PMT, respectively. At the 3‐year follow‐up, migraine‐specific direct costs were lower in the persistent subgroup relative to the non‐persistent subgroups in both AMT (mean [SD]: $789 [$1741] vs. $2847 [$8149] in the added‐on subgroup and $862 [$5426] for the cycled subgroup) and PMT cohorts (mean [SD]: $1817 [$5892] in the persistent subgroup vs. $4257 [$11,392] in the switched without gaps subgroup and $3269 [$18,540] in the cycled with gaps subgroup). Acute medication overuse was lower in the persistent subgroup (1025/6504 [27.2%]) vs. non‐persistent subgroups (11,236/58,863 [32.2%] in cycled with gaps subgroup and 1431/6504 [39.4%] in the switched without gaps subgroup). Most patients used multiple acute (19,717/20,778 [94.9%]) or preventive (38,494/42,259 [91.1%]) pharmacological therapies over 3 years following treatment initiation. Gaps in preventive therapy were common; an average gap ranged from 85 to 211 days (~3–7 months). Conclusion: Migraine‐specific annual healthcare costs and acute migraine medication overuse remained lowest among patients with persistent AMT and PMT versus non‐persistent treatment. Study findings are limited to the US population. Future studies should compare costs and associated outcomes between newer preventive migraine medications in patients with migraine. Plain Language Summary: Little is known about how patients use medications to acutely treat or prevent migraine over longer periods of time and their associated costs. This study used information from medical and pharmacy claims to understand costs over time for three groups of patients with migraine: (1) those who remained on the same medication for 3 years, (2) those who changed medications, or (3) those who stopped treatment and then changed medications. Results showed that fewer than one in 10 patients stayed on the same medication to treat or prevent migraine over 3 years, but migraine costs and acute migraine medication overuse were lowest in these patients. [ABSTRACT FROM AUTHOR]

Introduction Ambient air pollution has been associated with total mortality, as well as cardiorespiratory disease morbidity and mortality (Brook et al. 2010; Hoek et al. 2013). Recently, association between long-term [...], Background: Epidemiological studies have reported associations between particulate matter (PM) concentrations and cancer and respiratory and cardiovascular diseases. DNA methylation has been identified as a possible link but so far it has only been analyzed in candidate sites. Objectives: We studied the association between DNA methylation and short- and mid-term air pollution exposure using genome-wide data and identified potential biological pathways for additional investigation. Methods: We collected whole blood samples from three independent studies--KORA F3 (2004-2005) and F4 (2006-2008) in Germany, and the Normative Aging Study (1999-2007) in the United States--and measured genome-wide DNA methylation proportions with the Illumina 450k BeadChip. PM concentration was measured daily at fixed monitoring stations and three different trailing averages were considered and regressed against DNA methylation: 2-day, 7-day and 28-day. Meta-analysis was performed to pool the study-specific results. Results: Random-effect meta-analysis revealed 12 CpG (cytosine-guanine dinucleotide) sites as associated with PM concentration (1 for 2-day average, 1 for 7-day, and 10 for 28-day) at a genome-wide Bonferroni significance level (p ≤ 7.5E-8); 9 out of these 12 sites expressed increased methylation. Through estimation of [I.sup.2] for homogeneity assessment across the studies, 4 of these sites (annotated in NSMAF, C1orf2l2, MSGN1, NXN) showed p > 0.05 and [I.sup.2] < 0.5: the site from the 7-day average results and 3 for the 28-day average. Applying false discovery rate, p-value < 0.05 was observed in 8 and 1,819 additional CpGs at 7- and 28-day average [PM.sub.2.5] exposure respectively. Conclusion: The PM-related CpG sites found in our study suggest novel plausible systemic pathways linking ambient PM exposure to adverse health effect through variations in DNA methylation. http://dx.doi.org/10.1289/ehp.1509966

Objective: Metformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin.Research Design and Methods: We analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on metabolite concentrations, we quantified 131 metabolites in fasting serum samples and used multivariable linear regression models in three independent cross-sectional studies (n = 151 patients with T2D treated with metformin [mt-T2D]). Additionally, we used linear mixed-effect models to study the longitudinal KORA samples (n = 912) and performed mediation analyses to investigate the effects of metformin intake on blood lipid profiles. We combined genotyping data with the identified metformin-associated metabolites in KORA individuals (n = 1,809) and explored the underlying pathways.Results: We found significantly lower (P < 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. These findings were controlled for conventional risk factors of T2D and replicated in two independent studies. Furthermore, we observed that the levels of these metabolites decreased significantly in patients after they started metformin treatment during 7 years' follow-up. The reduction of these metabolites was also associated with a lowered blood level of LDL cholesterol (LDL-C). Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target.Conclusions: Our results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C. Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease. [ABSTRACT FROM AUTHOR]

INTRODUCTION:Health Technology Assessment (HTA) processes have become a fundamental part in the lifecycle of new medicines. However, their deep relation with national legislation creates ambiguous and controversial results between the European countries. Can they be standardized across Europe?METHODS:Sources of national differences have been identified in timelines, documents, methods, data interpretation, and conclusions. In order to harmonize and standardize HTA cooperation across Europe the European Network for HTA (EUnetHTA) was established. We analyzed guidelines, requirements, and output of EUnetHTA and noted the differences between those guidelines and the German G-BA (Federal Joint Committee, Gemeinsamer Bundesausschuss) standard and IQWiG (Institute for Quality and Efficiency in Health Care, Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen) methods.RESULTS:The comparison between German and European HTAs highlights that although both procedures follow the rules of Evidence-Based Medicine, differences in Body of Evidence, Comparator, Surrogate Endpoints, Subgroups, and Evidence Synthesis may lead to diverging HTA outcomes. The European HTA framework facilitates the appropriate depiction of clinical reality through comprehensive inclusion of the existing evidence with context specific statistical methods. It might become a worldwide platform for HTA evaluation and discussion.CONCLUSIONS:Only the involvement of both, pharmaceutical companies and HTA bodies within a unified European framework can lead to a mature and transparent procedure with a reliable outcome independent of legal requirements. [ABSTRACT FROM PUBLISHER]

Background: Fatigue is a burdensome, under-recognized, multidimensional symptom experienced by patients with Crohn's disease (CD). We evaluated the impact of mirikizumab on fatigue and the association between changes in select patient-reported outcomes and clinical measures with changes in fatigue from baseline to week 104 (W104)., Methods: Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200 mg, 600 mg, or 1000 mg of mirikizumab, administered intravenously (IV) every 4 weeks at W0, W4, and W8. Patients who achieved ≥1 point improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD) and received mirikizumab at W12 (rerandomized maintenance cohort) were rerandomized to continue induction IV treatment assignment (IV-C) or received 300 mg of mirikizumab subcutaneously (SC) until W52. Nonrandomized maintenance cohort had endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg of mirikizumab until W52. Subjects from the maintenance period with clinical benefit received 300 mg SC Q4W from W52 to W104. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire was used to assess fatigue, and the FACIT-F associations were assessed using Pearson correlation coefficient., Results: At W12, mirikizumab groups reported improved FACIT-F scores compared with PBO, and improvement was maintained through W52 and W104. Changes in FACIT-F at W52 and W104 had strong correlations with changes at the same time point in quality of life (QoL) scores but lacked correlations with changes in inflammatory biomarkers., Conclusions: Mirikizumab treatment significantly improved fatigue in patients with moderately to severely active CD, which was sustained to W104. The improvement in fatigue was correlated with improvement in clinical measures and was strongly correlated with improvement in QoL., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)