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Masahito Katsuki,1,2 Maiko Nanri,3 Yuki Miyakoshi,4 Shuto Gobo,4 Akihito Koh,2 Shin Kawamura,2 Senju Tachikawa,2 Ryo Matsukawa,2 Kenta Kashiwagi,5 Mitsuhiro Matsuo,6 Fuminori Yamagishi7 1Department of Neurosurgery and Headache Outpatient, Japanese Red Cross Suwa Hospital, Nagano, Japan; 2Department of Neurosurgery, Itoigawa General Hospital, Niigata, Japan; 3Nurse-Senka, SMS Corporation, Tokyo, Japan; 4Creatone, Regnition, Saitama, Japan; 5Department of Neurology, Itoigawa General Hospital, Niigata, Japan; 6Department of Anesthesiology, Toyama University Hospital, Toyama, Japan; 7Department of Surgery, Itoigawa General Hospital, Niigata, JapanCorrespondence: Masahito Katsuki, Department of Neurosurgery, Japanese Red Cross Suwa Hospital, 5-11-50, Kogandori, Suwa, Nagano, 392-0027, Japan, Tel/Fax +81-0266-52-6111, Email ktk1122nigt@gmail.comIntroduction: Headache is a common public health problem, but its burden could be avoided by raising headache awareness and the appropriate use of acute medication and prophylactic medication. Few reports on raising headache awareness in the general public have been reported, and there are no reports on headache awareness campaigns through social networking services (SNS), or social media, in Japan. We prospectively performed a headache awareness campaign from March 2022 through 2 SNS, targeting nurse and wind instrumental musicians, because they are with high headache prevalence.Methods: Through the 2 SNS, the article and video were distributed, respectively. The article and video described the 6 important topics for the general public about headaches, which were described in the Clinical Practice Guideline for Headache Disorders 2021. Just after reading or watching them as e-learning, we performed online questionnaire sheets to investigate the awareness of the 6 topics through the 2 SNS. The awareness of the 6 topics before and after the campaign was evaluated.Results: In the SNS nurse-senka, we obtained 1191 responses. Women comprised 94.4%, and the median (range) age was 45 (20 to 71) years old. Headache sufferers were 63.8%, but only 35.1% had consulted doctors. In the SNS Creatone, we got the response from 134 professional musicians, with 77.3% of women. The largest number of respondents were in their 20s (range 18– 60 years old). Headache sufferers were 87.9%. Of them, 36.4% had consulted doctors, 24.2% were medication-overuse headache. The ratios of individuals who were aware of the 6 topics significantly increased from 15.2%-47.0% to 80.4– 98.7% after the online questionnaire in both SNS (p < 0.001, all).Conclusion: E-learning and online survey via SNS can improve headache awareness.Keywords: awareness, education, medication-overuse headache, migraine, online, prevention, social networking services, social media

Triacylglycerol feeding in rats increases serum intestinal alkaline phosphatase (IAP) levels and results in the peak appearance of an alkaline phosphatase-containing particle in the lamina propria. This appearance is initially followed by peak concentrations in the serum and lumen. Lamina propria functions as a reservoir and is involved in the extracellular processing of surfactant-like particles (SLP). SLP are synthesized in the enterocyte and are diffused after fat feeding from the basolateral membrane in lamina propria. They migrate to intestinal lumen and finally to the serum.

Proteins associated with surfactant-like particle (SLP) are cleared from the blood of rats by the liver cells. SLP is obtained from the apical enterocytes of rat. The proteins differ from each other in their half-life values. The particles bind to hepatic basolateral membranes, with maximum binding capacity of 56 nanomoles per milligram.

The tuberculin skin test for immunologic diagnosis of Mycobacterium tuberculosis infection has many limitations, including being confounded by bacillus Calmette-Guérin (BCG) vaccination or exposure to nontuberculous mycobacteria. M. tuberculosis-specific antigens that are absent from BCG and most nontuberculous mycobacteria have been identified. We examined the use of two of these antigens, CFP-10 and ESAT-6, in a whole blood IFN-gamma assay as a diagnostic test for tuberculosis in BCG-vaccinated individuals. Because of the lack of an accurate standard with which to compare new tests for M. tuberculosis infection, specificity of the whole blood IFN-gamma assay was estimated on the basis of data from people with no identified risk for M. tuberculosis exposure (216 BCG-vaccinated Japanese adults) and sensitivity was estimated on the basis of data from 118 patients with culture-confirmed M. tuberculosis infection who had received less than 1 week of treatment. Using a combination of CFP-10 and ESAT-6 responses, the specificity of the test for the low-risk group was 98.1% and the sensitivity for patients with M. tuberculosis infection was 89.0%. The results demonstrate that the whole blood IFN-gamma assay using CFP-10 and ESAT-6 was highly specific and sensitive for M. tuberculosis infection and was unaffected by BCG vaccination status. [ABSTRACT FROM AUTHOR]

Abstract Background Although a variety of animals have been used to produce polyclonal antibodies against antigens, the production of antigen-specific monoclonal antibodies from animals remains challenging. Results We propose a simple and rapid strategy to produce monoclonal antibodies from a variety of animals. By staining lymph node cells with an antibody against immunoglobulin and a fluorescent dye specific for the endoplasmic reticulum, plasma/plasmablast cells were identified without using a series of antibodies against lineage markers. By using a fluorescently labeled antigen as a tag for a complementary cell surface immunoglobulin, antigen-specific plasma/plasmablast cells were sorted from the rest of the cell population by fluorescence-activated cell sorting. Amplification of cognate pairs of immunoglobulin heavy and light chain genes followed by DNA transfection into 293FT cells resulted in the highly efficient production of antigen-specific monoclonal antibodies from a variety of immunized animals. Conclusions Our technology eliminates the need for both cell propagation and screening processes, offering a significant advantage over hybridoma and display strategies.

Objective: To investigate the prescription patterns for patients aged 6-17 years with headaches in the REZULT database., Methods: We cross-sectionally investigated (Study 1) the pattern of prescription and the proportion of triptan overprescription (≥30 tablets/90 d of triptans) among patients diagnosed with headaches in 2020. Next, we longitudinally studied patients (Study 2) for more than two years from the initial headache diagnosis (July 2010 to April 2022). The number of prescribed tablets was counted every 90 days., Results: In Study 1, headache diagnoses were assigned to 62,568 of 543,628 (11.51%) patients, and 1524 of 62,568 (2.44%) patients received acute medication. Single nonsteroidal anti-inflammatory drugs and triptans were prescribed to 620/624 (99.36%) and 5/624 (0.80%) of patients aged 6-11 years, respectively, and 827/900 (91.89%) and 91/900 (10.11%) of patients aged 12-17 years, respectively. Triptan overprescription was observed in 11/96 (11.46%) patients, and 5/11 (45.45%) of those patients received prophylactic medication. In Study 2, 80,756/845,470 (9.55%) patients aged 6-17 years were diagnosed with headaches that persisted for at least two years. Over two years, 44/80,756 (0.05%) patients were overprescribed triptans, and 3408/80,756 (4.22%) patients were prescribed prophylaxis on at least one occasion., Conclusions: Based on real-world data, the appropriate use of prophylactic treatment is still problematic. Overprescription of triptans was observed, although the number of patients was small.

Background: The present study aimed to investigate prescription patterns for patients aged over 17 years with headaches in the REZULT database., Methods: We conducted a cross-sectional study (Study 1) of the proportion of over-prescription of acute medications (≥30 tablets/90 days for triptans, combination non-steroidal anti-inflammatory drugs (NSAIDs) and multiple types; ≥45 tablets/90 days for single NSAIDs) among patients with headache diagnosed in 2020. We longitudinally studied (Study 2) patients for >2 years from initial headache diagnosis (July 2010 to April 2022). The number of prescribed tablets was counted every 90 days., Results: In Study 1, headache was diagnosed in 200,055 of 3,638,125 (5.5%) patients: 13,651/200,055 (6.8%) received acute medication. Single NSAIDs were prescribed to 12,297/13,651 (90.1%) patients and triptans to 1710/13,651 (12.5%). Over-prescription was found in 2262/13,651 (16.6%) patients and 1200/13,651 (8.8%) patients received prophylactic medication. In Study 2, 408,183/6,840,618 (6.0%) patients were first diagnosed with headaches, which persisted for ≥2 years. Over time, the proportion of patients over-prescribed acute medications increased. Over 2 years, 37,617/408,183 (9.2%) patients were over-prescribed acute medications and 29,313/408,183 (7.2%) patients were prescribed prophylaxis at least once., Conclusions: According to real-world data, prophylaxis remains poorly prescribed, and both acute and prophylactic treatment rates for headaches have increased over time., Competing Interests: Declaration of conflicting interestsMasahito Katsuki received personal consultancy fees from Amgen Astellas BioPharma K.K., Daiichi Sankyo Company, Limited, Eli Lilly Japan K.K. and Otsuka Pharmaceutical Co., Ltd. during the conduct of the study.Yasuhiko Matsumori received personal consultancy fees from Amgen Astellas BioPharma K.K., Daiichi Sankyo Company, Limited, Eli Lilly Japan K.K. and Otsuka Pharmaceutical Co., Ltd. during the conduct of the study.Taisuke Ichihara and Yuya Yamada are employees of Japan System Techniques Co. Ltd.Keiichi Kaneko and Yasushi Kobayashi are employees in Bio-Medicines, Japan Drug Development & Medical Affairs at Eli Lilly Japan K.K. and own minor shares in Eli Lilly and Company.The other authors report no conflicts of interest concerning the materials or methods used in this study or the findings presented in this paper. This article and contents of this study were not published nor presented previously.

Objective: We developed an artificial intelligence (AI)-based headache diagnosis model using a large questionnaire database from a headache-specializing clinic., Background: Misdiagnosis of headache disorders is a serious issue and AI-based headache diagnosis models are scarce., Methods: We developed an AI-based headache diagnosis model and conducted internal validation based on a retrospective investigation of 6058 patients (4240 training dataset for model development and 1818 test dataset for internal validation) diagnosed by a headache specialist. The ground truth was the diagnosis by the headache specialist. The diagnostic performance of the AI model was evaluated., Results: The dataset included 4829/6058 (79.7%) patients with migraine, 834/6058 (13.8%) with tension-type headache, 78/6058 (1.3%) with trigeminal autonomic cephalalgias, 38/6058 (0.6%) with other primary headache disorders, and 279/6058 (4.6%) with other headaches. The mean (standard deviation) age was 34.7 (14.5) years, and 3986/6058 (65.8%) were female. The model's micro-average accuracy, sensitivity (recall), specificity, precision, and F-values for the test dataset were 93.7%, 84.2%, 84.2%, 96.1%, and 84.2%, respectively. The diagnostic performance for migraine was high, with a sensitivity of 88.8% and c-statistics of 0.89 (95% confidence interval 0.87-0.91)., Conclusions: Our AI model demonstrated high diagnostic performance for migraine. If secondary headaches can be ruled out, the model can be a powerful tool for diagnosing migraine; however, further data collection and external validation are required to strengthen the performance, ensure the generalizability in other outpatients, and demonstrate its utility in real-world settings., (© 2023 American Headache Society.)

Introduction Misdiagnosis of pediatric and adolescent migraine is a significant problem. The first artificial intelligence (AI)-based pediatric migraine diagnosis model was made utilizing a database of questionnaires obtained from a previous epidemiological study, the Itoigawa Benizuwaigani Study. Methods The AI-based headache diagnosis model was created based on the internal validation based on a retrospective investigation of 909 patients (636 training dataset for model development and 273 test dataset for internal validation) aged six to 17 years diagnosed based on the International Classification of Headache Disorders 3rd edition. The diagnostic performance of the AI model was evaluated. Results The dataset included 234/909 (25.7%) pediatric or adolescent patients with migraine. The mean age was 11.3 (standard deviation 3.17) years. The model's accuracy, sensitivity (recall), specificity, precision, and F-values for the test dataset were 94.5%, 88.7%, 96.5%, 90.0%, and 89.4%, respectively. Conclusions The AI model exhibited high diagnostic performance for pediatric and adolescent migraine. It holds great potential as a powerful tool for diagnosing these conditions, especially when secondary headaches are ruled out. Nonetheless, further data collection and external validation are necessary to enhance the model's performance and ensure its applicability in real-world settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sasaki et al.)

Introduction Raising stroke awareness is important to shorten the interval from onset to consultation. We performed a school-based stroke education by on-demand e-learning during the coronavirus disease 2019 pandemic. Methods We performed on-demand e-learning and distributed the online- and paper-based manga about stroke for students and parental guardians in August 2021. We carried out this in a manner similar to the prior effective online stroke awareness initiatives in Japan. An online post-educational survey in October 2021 was conducted to evaluate the awareness effects by asking participants about their knowledge. We also investigated the modified Rankin Scale (mRS) at the discharge of stroke patients who were treated in our hospital during the before- and after-campaign periods, respectively. Results We distributed the paper-based manga and asked to work on this campaign to all 2,429 students (1,545 elementary school and 884 junior high school students) who lived in Itoigawa. We acquired 261 (10.7%) online responses from the students and 211 (8.7%) responses from their parental guardians. The number of students who chose all correct answers in the survey significantly increased after the campaign (205/261, 78.5%) compared to that before the campaign (135/261, 51.7%) and those of parental guardians showed similar trends (before campaign 93/211, 44.1%; after campaign 198/211, 93.8%). We investigated 282 stroke patients (90 patients before and 192 patients after-campaign period), and their mRS at discharge after-campaign seemed to be improved. Conclusion Only 10.7% of students and 8.7% of the parental guardians worked on the online survey. However, the number of those who chose correct answers about stroke increased after the campaign. After this campaign, the mRS of stroke patients at discharge improved although it was unclear if this is a direct result of this activity., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Katsuki et al.)

Background: We investigated the prevalence of headache, migraine, and medication-overuse headache (MOH) among children and adolescents through a school-based online questionnaire. We also investigated the triggers for migraine among them and the effect of the COVID-19 pandemic on headache frequency., Methods: Children and adolescents aged 6-17 y.o. completed an online questionnaire. Migraine, MOH was defined as The International Classification of Headache Disorders Third edition. Factor and clustering analyses were performed for migraine triggers. The effect of the coronavirus disease 2019 (COVID-19) pandemic on headache frequency was also asked., Results: Of the 2489 respondents, the prevalence of headache, migraine, and MOH were 36.44%, 9.48%, and 0.44%, respectively. Up to 70% of the respondents with headaches complained of the disturbance to daily life, but about 30% consulted doctors. The migraine triggers were grouped into 5 factors by factor analysis. The sensitivities of the migraineurs against the factors were divided into 3 clusters. Cluster 1 had stronger sensitivity for several triggers. Cluster 2 was sensitive to weather, smartphones, and video games. Cluster 3 had less sensitivity for triggers. Cluster 2 less consulted doctors even though the burden of migraine was enormous. During the COVID-19 pandemic, 10.25% of respondents increased headache attacks, while 3.97% decreased., Conclusions: This is the first detailed study on headache prevalence in Japanese students from elementary school to high school in one region. The burden of headaches is large among children and adolescents, and the unmet needs of its clinical practice should be corrected., Competing Interests: Conflict of interest statement This research has never been presented at a conference. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: We prospectively performed the Itoigawa Headache Awareness Campaign from August 2021 to June 2022, with two main interventions, and evaluated its effectiveness., Background: Headache is a common public health problem, but its burden could be reduced by raising awareness about headache and the appropriate use of acute and prophylactic medication. However, few studies on raising headache awareness in the general public have been reported., Methods: The target group was the general public aged 15-64. We performed two main interventions synergistically supported by other small interventions. Intervention 1 included leaflet distribution and a paper-based questionnaire about headache during COVID-19 vaccination, and intervention 2 included on-demand e-learning and online survey through schools. In these interventions, we emphasize the six important topics for the general public that were described in the Clinical Practice Guideline for Headache Disorders 2021. Each response among the two interventions' cohorts was collected on pre and post occasions. The awareness of the six topics before and after the campaign was evaluated., Results: We obtained 4016 valid responses from 6382 individuals who underwent vaccination in intervention 1 and 2577 from 594 students and 1983 parents in intervention 2; thus, 6593 of 20,458 (32.2%) of the overall working-age population in Itoigawa city experienced these interventions. The percentage of individuals' aware of the six topics significantly increased after the two main interventions ranging from 6.6% (39/594)-40.0% (1606/4016) to 64.1% (381/594)-92.6% (1836/1983) (p < 0.001, all)., Conclusions: We conducted this campaign through two main interventions with an improved percentage of individuals who know about headache. The two methods of community-based interventions could raise headache awareness effectively. Furthermore, we can achieve outstanding results by doing something to raise disease awareness during mass vaccination, when almost all residents gather in a certain place, and school-based e-learning without face-to-face instruction due to the COVID-19 pandemic., (© 2023 American Headache Society.)

Background: The prevalence of headache disorders, migraine, chronic daily headache (CDH), and medication-overuse headache (MOH) among the elderly in Japan has not been sufficiently investigated. We performed a questionnaire-based survey and revealed 3-month headache prevalence and headaches' characteristics., Methods: The population aged over 64 was investigated in Itoigawa during their third coronavirus disease 2019 vaccination. Migraine, MOH was defined as The International Classification of Headache Disorders Third edition. CDH was defined as a headache occurring at least 15 days per month. K-means++ were used to perform clustering., Results: Among 2858 valid responses, headache disorders, migraine, CDH, and MOH prevalence was 11.97%, 0.91%, 1.57%, and 0.70%, respectively. Combined-analgesic and non-opioid analgesic were widely used. Only one migraineur used prophylactic medication. We performed k-means++ to group the 332 MOH patients into four clusters. Cluster 1 seemed to have tension-type headache-like headache characteristics, cluster 2 seemed to have MOH-like headache characteristics, cluster 3 seemed to have severe headaches with comorbidities such as dyslipidemia, stroke, and depression, and cluster 4 seemed to have migraine-like headache characteristics with photophobia and phonophobia., Conclusions: This is the largest prevalence survey in the Japanese elderly. Headache disorders are still the elderly's burden. Clustering suggested that severe headaches associated with some comorbidities may be unique to the elderly.