Treatment patterns and characteristics of headache in patients in Japan: A retrospective cross-sectional and longitudinal analysis of health insurance claims data.

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.

Developing an artificial intelligence-based headache diagnostic model and its utility for non-specialists' diagnostic accuracy.

BACKGROUND: Misdiagnoses of headache disorders are a serious issue. Therefore, we developed an artificial intelligence-based headache diagnosis model using a large questionnaire database in a specialized headache hospital. METHODS: Phase 1: We developed an artificial intelligence model based on a retrospective investigation of 4000 patients (2800 training and 1200 test dataset) diagnosed by headache specialists. Phase 2: The model's efficacy and accuracy were validated. Five non-headache specialists first diagnosed headaches in 50 patients, who were then re-diagnosed using AI. The ground truth was the diagnosis by headache specialists. The diagnostic performance and concordance rates between headache specialists and non-specialists with or without artificial intelligence were evaluated. RESULTS: Phase 1: The model's macro-average accuracy, sensitivity (recall), specificity, precision, and F values were 76.25%, 56.26%, 92.16%, 61.24%, and 56.88%, respectively, for the test dataset. Phase 2: Five non-specialists diagnosed headaches without artificial intelligence with 46% overall accuracy and 0.212 kappa for the ground truth. The statistically improved values with artificial intelligence were 83.20% and 0.678, respectively. Other diagnostic indexes were also improved. CONCLUSIONS: Artificial intelligence improved the non-specialist diagnostic performance. Given the model's limitations based on the data from a single center and the low diagnostic accuracy for secondary headaches, further data collection and validation are needed.

Investigating the effects of weather on headache occurrence using a smartphone application and artificial intelligence: A retrospective observational cross-sectional study.

OBJECTIVE: To investigate the relationship between weather and headache occurrence using big data from an electronic headache diary smartphone application with recent statistical and deep learning (DL)-based methods. BACKGROUND: The relationship between weather and headache occurrence remains unknown. METHODS: From a database of 1 million users, data from 4375 users with 336,951 hourly headache events and weather data from December 2020 to November 2021 were analyzed. We developed statistical and DL-based models to predict the number of hourly headache occurrences mainly from weather factors. Temporal validation was performed using data from December 2019 to November 2020. Apart from the user dataset used in this model development, the physician-diagnosed headache prevalence was gathered. RESULTS: Of the 40,617 respondents, 15,127/40,617 (37.2%) users experienced physician-diagnosed migraine, and 2458/40,617 (6.1%) users had physician-diagnosed non-migraine headaches. The mean (standard deviation) age of the 4375 filtered users was 34 (11.2) years, and 89.2% were female (3902/4375). Lower barometric pressure (p < 0.001, gain = 3.9), higher humidity (p < 0.001, gain = 7.1), more rainfall (p < 0.001, gain = 3.1), a significant decrease in barometric pressure 6 h before (p < 0.001, gain = 11.7), higher barometric pressure at 6:00 a.m. on the day (p < 0.001, gain = 4.6), lower barometric pressure on the next day (p < 0.001, gain = 6.7), and raw time-series barometric type I (remaining low around headache attack, p < 0.001, gain = 10.1) and type II (decreasing around headache attack, p < 0.001, gain = 10.1) changes over 6 days, were significantly associated with headache occurrences in both the statistical and DL-based models. For temporal validation, the root mean squared error (RMSE) was 13.4, and the determination coefficient (R2 ) was 52.9% for the statistical model. The RMSE was 10.2, and the R2 was 53.7% for the DL-based model. CONCLUSIONS: Using big data, we found that low barometric pressure, barometric pressure changes, higher humidity, and rainfall were associated with an increased number of headache occurrences.

Developing an artificial intelligence-based diagnostic model of headaches from a dataset of clinic patients' records.

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.

Headache education by leaflet distribution during COVID-19 vaccination and school-based on-demand e-learning: Itoigawa Geopark Headache Awareness Campaign.

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.

Association between intraoperative pulmonary artery pressure and cardiovascular complications after off-pump coronary artery bypass surgery: a single-center observational study.

BACKGROUND: The impact of intraoperative pulmonary hemodynamics on prognosis after off-pump coronary artery bypass (OPCAB) surgery remains unknown. In this study, we examined the association between intraoperative vital signs and the development of major adverse cardiovascular events (MACE) during hospitalization or within 30 days postoperatively. METHODS: This retrospective study analyzed data from a university hospital. The study cohort comprised consecutive patients who underwent isolated OPCAB surgery between November 2013 and July 2021. We calculated the mean and coefficient of variation of vital signs obtained from the intra-arterial catheter, pulmonary artery catheter, and pulse oximeter. The optimal cut-off was defined as the receiver operating characteristic curve (ROC) with the largest Youden index (Youden index = sensitivity + specificity - 1). Multivariate logistic regression analysis ROC curves were used to adjust all baseline characteristics that yielded P values of < 0.05. RESULTS: In total, 508 patients who underwent OPCAB surgery were analyzed. The mean patient age was 70.0 ± 9.7 years, and 399 (79%) were male. There were no patients with confirmed or suspected preoperative pulmonary hypertension. Postoperative MACE occurred in 32 patients (heart failure in 16, ischemic stroke in 16). The mean pulmonary artery pressure (PAP) was significantly higher in patients with than without MACE (19.3 ± 3.0 vs. 16.7 ± 3.4 mmHg, respectively; absolute difference, 2.6 mmHg; 95% confidence interval, 1.5 to 3.8). The area under the ROC curve of PAP for the prediction of MACE was 0.726 (95% confidence interval, 0.645 to 0.808). The optimal mean PAP cut-off was 18.8 mmHg, with a specificity of 75.8% and sensitivity of 62.5% for predicting MACE. After multivariate adjustments, high PAP remained an independent risk factor for MACE. CONCLUSIONS: Our findings provide the first evidence that intraoperative borderline pulmonary hypertension may affect the prognosis of patients undergoing OPCAB surgery. Future large-scale prospective studies are needed to verify the present findings.

Questionnaire-based survey on the prevalence of medication-overuse headache in Japanese one city-Itoigawa study.

OBJECTIVE: The medication-overuse headache (MOH) prevalence has not been investigated in a general Japanese population. We performed questionnaire-based survey and revealed MOH prevalence and its characteristics. We also performed clustering to obtain insight for MOH subgrouping. METHODS: In this cross-sectional study, the 15-64-year-old population was investigated in Itoigawa during their COVID-19 vaccination under the national policy. MOH was defined as ≥ 15 days/month plus self-report of use of pain medications ≥ 10 or 15 days/month in the last 3 months. Ward method and k-means + + were used to perform clustering MOH patients. RESULTS: Among 5865 valid responses, MOH prevalence was 2.32%. MOH was common among females and the middle-aged. Combination-analgesic is the most overused as 50%. MOH had aggravation by routine physical activity, moderate or severe pain, and migraine-like, compared to non-MOH. The 136 MOH patients could be grouped into 3 clusters. Age and frequency of acute medication use were essential factors for clustering. CONCLUSIONS: This is the first study of MOH prevalence in Japan. Most MOH characteristics were similar to previous reports worldwide. Public awareness of proper headache treatment knowledge is still needed. Clustering results may be important for subtype grouping from a social perspective apart from existing clinical subtypes.

Musician developed left putaminal hemorrhage and lost absolute pitch ability-case report.

Absolute pitch (AP) recognizes and labels the pitch chroma of a given tone without external reference. Its neural mechanism remains unclear. We report a 68-year-old AP musician who developed a left putaminal hemorrhage edematous lesion under the posterior insular cortex. Diffusion tensor tractography with the region of interest, including Heschl's gyrus, was performed. In the left hemisphere, the middle longitudinal fasciculus was absent, especially at the parietal lobe. Her AP ability was lost. As the hematoma was absorbed and the left MdLF was observed on the tractography, her AP ability recovered. Our case suggested that the left middle longitudinal fasciculus, a part of the ventral auditory pathway, plays a role in AP.

Pre-operative higher hematocrit and lower total protein levels are independent risk factors for cerebral hyperperfusion syndrome after superficial temporal artery-middle cerebral artery anastomosis with pial synangiosis in adult moyamoya disease patients-case-control study.

Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is a standard treatment for adult moyamoya disease (MMD) patients. Cerebral hyperperfusion (CHP) syndrome is one of the most serious complications of this procedure that can result in deleterious outcomes, but predicting CHP before revascularization surgery remains challenging. Furthermore, the hematological/serological factors associated with CHP syndrome are unknown. To investigate the correlation between pre-operative hematological/serological factors and the development of CHP syndrome after STA-MCA anastomosis with encephalo-duro-myo-synangiosis (EDMS) for MMD., a pre-operative peripheral blood test was performed within 5 days before surgery. Local cerebral blood flow (CBF) at the site of anastomosis was quantified by N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, and the pre-operative CBF value at the corresponding area was measured. We defined CHP syndrome as a local CBF increase over 150% compared with the pre-operative value, which was responsible for delayed intracranial hemorrhage, transient focal neurological deterioration, and/or seizure. Then, we retrospectively investigated the correlation between peripheral blood test results and the development of CHP syndrome. CHP syndrome 1 day after STA-MCA anastomosis with EDMS was observed in nine patients (9/114 hemispheres; 7.9%). Multivariate analysis with multiple imputation revealed that higher hematocrit value and lower total protein level were significantly associated with the development of CHP syndrome (p value: 0.028 and 0.043, respectively). Higher pre-operative hematocrit levels and lower pre-operative total protein levels are novel risk factors for CHP syndrome after direct revascularization surgery in adult MMD patients.

Prediction of Cerebral Hyperperfusion after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis by Three-Dimensional-Time-of-Flight Magnetic Resonance Angiography in Adult Patients with Moyamoya Disease.

INTRODUCTION: Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is an effective surgical procedure for adult patients with moyamoya disease (MMD) and is known to have the potential to prevent cerebral ischemia and/or hemorrhagic stroke. Cerebral hyperperfusion (CHP) syndrome is one of the serious complications of this procedure that can result in deleterious outcomes, such as delayed intracerebral hemorrhage, but the prediction of CHP before revascularization surgery remains challenging. The present study evaluated the diagnostic value of preoperative three-dimensional (3D)-time-of-flight (TOF) magnetic resonance angiography (MRA) for predicting CHP after STA-MCA anastomosis for MMD. MATERIALS AND METHODS: The signal intensity of the peripheral portion of the intracranial major arteries, such as the anterior cerebral artery (ACA), MCA, and posterior cerebral artery (PCA) ipsilateral to STA-MCA anastomosis, on preoperative MRA was graded (0-2 in each vessel) according to the ability to visualize each vessel on 97 affected hemispheres in 83 adult MMD patients. Local cerebral blood flow (CBF) at the site of anastomosis was quantitatively measured by N-isopropyl-p-[123I]-iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, in addition to the preoperative CBF value at the corresponding area. Then, we investigated the correlation between the preoperative MRA score and the development of CHP. RESULTS: The CHP phenomenon 1 day after STA-MCA anastomosis (local CBF increase over 150% compared with the preoperative value) was evident in 27 patients (27/97 hemispheres; 28%). Among them, 8 (8 hemispheres) developed CHP syndrome. Multivariate analysis revealed that the hemispheric MRA score (0-6), the summed ACA, MCA, and PCA scores for the affected hemisphere, was significantly associated with the development of CHP syndrome (p = 0.011). The hemispheric MRA score was also significantly correlated with the CHP phenomenon, either symptomatic or asymptomatic (p < 0.001). CONCLUSION: The signal intensity of the intracranial major arteries, including the ACA, MCA, and PCA, on preoperative 3D-TOF MRA may identify adult MMD patients at higher risk for CHP after direct revascularization surgery.

Lower total protein and absence of neuronavigation are novel poor prognostic factors of endoscopic hematoma removal for intracerebral hemorrhage.

OBJECTIVES: Endoscopic hematoma removal is widely performed for the treatment of intracerebral hemorrhage. We investigated the factors related to the prognosis of intracerebral hemorrhage after endoscopic hematoma removal. MATERIALS AND METHODS: From 2013 to 2019, we retrospectively analyzed 75 consecutive patients with hypertensive intracerebral hemorrhage who underwent endoscopic hematoma removal. Their characteristics, including neurological symptoms, laboratory data, and radiological findings were investigated using univariate and multivariate analysis. Complications during hospitalization, Glasgow Coma Scale (GCS) score on day 7, and modified Rankin Scale (mRS) score at 6 months were considered as treatment outcomes. RESULTS: The mean age of the patients (33 women, 42 men) was 71.8 (36-95) years. Mean GCS scores at admission and on day 7 were 10.3 ± 3.2 and 11.7 ± 3.8, respectively. The mean mRS score at 6 months was 3.8 ± 1.6, and poor outcome (mRS score ranging from 3 to 6 at 6 months) in 53 patients. Rebleeding occurred in 4 patients, and other complications in 15 patients. Multivariate analysis revealed that older age, hematoma in the basal ganglia, lower total protein level, higher glucose level, and absence of neuronavigation were associated with poor outcomes. Of the 75 patients, 9 had cerebellar hemorrhages, and they had relatively favorable outcomes compared to those with supratentorial hemorrhages. CONCLUSION: Several factors were related to the prognosis of intracerebral hemorrhage after endoscopic hematoma removal. Lower total protein level at admission and absence of neuronavigation were novel factors related to poor outcomes of endoscopic hematoma removal for intracerebral hemorrhage.

A Case of Headache Treated by Online Telemedicine in Collaboration With a Midwifery Home.

Midwifery centers are places where midwives not only provide antenatal checkups and delivery care but also offer a wide range of health guidance to pregnant women, postpartum mothers, newborns, and older women. In recent years, midwives have also provided onsite and online health guidance. However, diagnosis and prescribing medication are impossible in midwifery centers because no doctor is present. If the midwife determines that the patient should consult doctors, the patient may have to go to a hospital and see doctors in person, which can be burdensome. Online telemedicine facilitates midwife-doctor collaboration and may solve this problem. We report a case of headache management by telemedicine that minimized the patient's travel burden by collaborating with a midwifery center that provides onsite, visiting, and online health guidance for patients who have difficulty visiting a hospital due to postpartum period, childcare, and breastfeeding. A 29-year-old woman and her husband were raising an infant in Sado City (a remote island across the sea), Niigata Prefecture. She developed acute back pain and was bedridden for several days due to immobility. She consulted a midwife because of stress and anxiety caused by childcare and acute back pain, as well as newly occurring headaches. The midwife visited her and provided on-site health guidance. The midwife decided that a doctor's diagnosis and treatment with painkillers were desirable for the headache and back pain, so she contacted a doctor based on the patient's request. The doctor provided online telemedicine across the sea, diagnosed her headache as a tension-type headache, and prescribed acetaminophen 500 mg as an abortive prescription. The prescription was faxed to a pharmacy on the island, and the original was sent by post. The midwife picked up the medication and delivered it to the patient. After taking the medication, the patient's back pain and headache went into remission. Collaboration between midwifery centers that provide onsite, visiting, and online health guidance and medical institutions that offer online telemedicine can potentially improve accessibility to medical care. It differs from conventional online telemedicine in the midwife's coordination practice by monitoring the patient's condition and requesting the physician based on the patient's request.

Anodal Electrical Taste Stimulation to the Chin Enhances the Salt Taste Perception in Subarachnoid Hemorrhage Patients.

Aneurysmal subarachnoid hemorrhage (SAH) is a critical condition associated with high mortality rates. Hypertension is a significant risk factor for SAH development and recurrence following coil embolization for a ruptured aneurysm. While reduction of salt consumption is crucial for managing hypertension, it often compromises food taste. Anodal electrical taste stimulation (ETS) has been proposed to enhance taste perception without altering salt content. We present the case of a 69-year-old female SAH patient with a ruptured aneurysm at the anterior communicating artery who underwent coil embolization and in whom we tested ETS's efficacy in enhancing the salt taste perception on day 42 after the procedure. ETS effectively enhanced the salt taste perception threshold and perceived concentration; the threshold for salt taste without electrical stimulation was 0.8% of salt-impregnated filter paper, whereas that with electrical stimulation was 0.6%. The perception of salt taste was enhanced: 0.8% and 1.0% of filter papers were perceived as 0.6% and 0.8% without electrical stimulation and 1.0% and 1.2% with electrical stimulation, respectively. This is the first report describing the salt perception-enhancing effect of ETS in an actual patient. Further studies involving actual patients are required to determine how ETS affects habitual salt intake and blood pressure trends.

Treatment Patterns for and Characteristics of Headache in Children and Adolescents Aged 6-17 Years in Japan: A Retrospective Cross-Sectional and Longitudinal Analysis of Health Insurance Claims Data.

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.

Preliminary External Validation Results of the Artificial Intelligence-Based Headache Diagnostic Model: A Multicenter Prospective Observational Study.

The misdiagnosis of headache disorders is a serious issue, and AI-based headache model diagnoses with external validation are scarce. We previously developed an artificial intelligence (AI)-based headache diagnosis model using a database of 4000 patients' questionnaires in a headache-specializing clinic and herein performed external validation prospectively. The validation cohort of 59 headache patients was prospectively collected from August 2023 to February 2024 at our or collaborating multicenter institutions. The ground truth was specialists' diagnoses based on the initial questionnaire and at least a one-month headache diary after the initial consultation. The diagnostic performance of the AI model was evaluated. The mean age was 42.55 ± 12.74 years, and 51/59 (86.67%) of the patients were female. No missing values were reported. Of the 59 patients, 56 (89.83%) had migraines or medication-overuse headaches, and 3 (5.08%) had tension-type headaches. No one had trigeminal autonomic cephalalgias or other headaches. The models' overall accuracy and kappa for the ground truth were 94.92% and 0.65 (95%CI 0.21-1.00), respectively. The sensitivity, specificity, precision, and F values for migraines were 98.21%, 66.67%, 98.21%, and 98.21%, respectively. There was disagreement between the AI diagnosis and the ground truth by headache specialists in two patients. This is the first external validation of the AI headache diagnosis model. Further data collection and external validation are required to strengthen and improve its performance in real-world settings.

Thyroid hormone negatively regulates CDX2 and SOAT2 mRNA expression via induction of miRNA-181d in hepatic cells.

Thyroid hormones (THs) regulate transcription of many metabolic genes in the liver through its nuclear receptors (TRs). Although the molecular mechanisms for positive regulation of hepatic genes by TH are well understood, much less is known about TH-mediated negative regulation. Recently, several nuclear hormone receptors were shown to downregulate gene expression via miRNAs. To further examine the potential role of miRNAs in TH-mediated negative regulation, we used a miRNA microarray to identify miRNAs that were directly regulated by TH in a human hepatic cell line. In our screen, we discovered that miRNA-181d is a novel hepatic miRNA that was regulated by TH in hepatic cell culture and in vivo. Furthermore, we identified and characterized two novel TH-regulated target genes that were downstream of miR-181d signaling: caudal type homeobox 2 (CDX2) and sterol O-acyltransferase 2 (SOAT2 or ACAT2). CDX2, a known positive regulator of hepatocyte differentiation, was regulated by miR-181d and directly activated SOAT2 gene expression. Since SOAT2 is an enzyme that generates cholesteryl esters that are packaged into lipoproteins, our results suggest miR-181d plays a significant role in the negative regulation of key metabolic genes by TH in the liver.

Oxybutynin for Primary Palmer Hyperhidrosis Attenuates Migraine Attacks and Burdens.

Migraine is a neurological disorder with recurrent headaches accompanied by burdens in social life. Primary palmar hyperhidrosis is a chronic condition with excessive sweating of the palms that can significantly impair quality of life. Primary hyperhidrosis can cause anxiety, and stress, including anxiety, is the most common inducer of migraine headaches. Recently, oxybutynin has been used for primary palmar hyperhidrosis. We herein describe a 26-year-old female migraine patient with primary palmar hyperhidrosis whose migraine attacks and burdens were attenuated after the prescription of an oxybutynin lotion formula. The patient's monthly headache days (MHD) and monthly acute medication intake days (AMD) at the first visit were 10 and 9. Headache Impact Score 6 (HIT-6) at the initial visit was 63. After the prescription of Japanese herbal kampo medicine Goreisan (TJ-17), Goshuyuto (TJ-31), and 200 mg of valproic acid, MHD, AMD, and HIT-6 decreased gradually. However, these parameters could not improve sufficiently at nine months: MHD 4, AMD 4, and HIT-6 52. We first prescribed a lotion formulation of 20% oxybutynin hydrochloride at nine months. After this, migraine was further attenuated, and stress related to primary palmar hyperhidrosis was reduced; at 12 months, the patient had achieved MHD 2, AMD 2, and HIT-6 48. She will continue receiving primary palmar hyperhidrosis treatment while tapering off migraine prophylaxis. While the exact mechanisms connecting migraine and primary hyperhidrosis remain uncertain, this case raises important questions about the potential interplay between stress, sweating, and migraine triggers.

Monoclonal Antibodies Against the Calcitonin Gene-Related Peptide and Its Receptor in Japanese Adolescents With Migraines.

Introduction Adolescent migraines is a public health problem, and effective prophylactic treatment is needed. In Japan, three types of calcitonin gene-related peptide-related monoclonal antibodies (CGRP-mABs) are available. Galcanezumab, fremanezumab, and erenumab can be used for migraine prevention in ages 15 years or older, but reports on adolescent migraine treated with CGRP-mABs remain few. We described this study to report the real-world data of CGRP-mABs' efficacy for adolescents with migraines aged from 15 to 17 years old. Methods We retrospectively investigated ten adolescent migraine patients aged from 15 to 17 years old treated with CGRP-mABs. Headache impact test-6 (HIT-6), monthly headache days (MHD), and monthly acute medication intake days (AMD) before and three months after CGRP-mABs treatment were evaluated. Results Six females and four males were included. Seven had episodic migraines (EM), three had EM and tension-type headaches, one had chronic migraines (CM), and one had CM and medication-overuse headaches. As chief obstacles to life due to headaches, five reported them as detrimental to study, one reported them as detrimental to playing sports, and four reported missing school. The median HIT-6 was 63 (46-68) and 44 (36-65) before and three months after treatment, respectively. Median of MHD was 5.5 (1-29) and 1.5 (1-30), respectively, and the median of AMD was 5.5 (1-30) and 1 (0-30), respectively. A significant reduction of HIT-6 was observed at three months (p=0.008). Six (60%) of the ten patients experienced therapeutic effectiveness. Patients with missing school as the chief obstacle to life due to headaches seemed ineffective compared to those with other obstacles (p=0.048). There were no side effects of CGRP-mABs. Conclusion We herein described the ten adolescent migraine patients treated with CGRP-mABs. HIT-6 score significantly decreased at three months, and six of the ten patients experienced therapeutic effectiveness measured by HIT-6. Now several trials have been ongoing to test the efficacy of CGRP-mABs for adolescents. Urgent evidence accumulation is needed about CGRP-mABs for adolescents.

One-Time Use of Galcanezumab or Fremanezumab for Migraine Prevention.

Background There are no reports on the effectiveness of one-time use of the calcitonin gene-related peptide-related monoclonal antibodies (CGRP-mABs) evaluated at one and three months for migraine prevention. Here, we present the real-world data of one-time administration of CGRP-mABs, galcanezumab and fremanezumab, for migraine prevention. Methodology We retrospectively investigated eight migraine patients treated with one-time administration of galcanezumab 240 mg or fremanezumab 225 mg. Monthly headache days (MHD), monthly acute medication intake days (AMD), and Headache Impact Test-6 (HIT-6) scores before, one, and three months after one-time CGRP-mABs administration were evaluated. Results A total of five women and three men were included (median age = 46.5 years, range = 19-63 years). Overall, six were episodic migraine, and two were chronic migraine. Five patients received one-time administration of fremanezumab and three received galcanezumab. In total, six (75.0%) patients experienced therapeutic effectiveness one month after the one-time administration. Five of the six maintained the therapeutic effect until three months, but one had aggravation. As a result, six (75.0%) patients reached or maintained therapeutic conditions three months after the one-time administration of CGRP-mABs without side effects. All patients continued previously used oral prophylaxis during the observational period. Significant reductions in MHD, AMD, and HIT-6 scores were observed three months after the initial administration (p = 0.008, p = 0.005, and p < 0.001, respectively). Conclusions Six of the eight patients experienced or maintained therapeutic effectiveness at three months despite the one-time administration of CGRP-mABs. Our results suggest that one-time use of CGRP-mABs may be a new treatment option in combination with oral prophylaxis.

Efficacy of Kampo medicine Kakkonto as acute medication to treat tension-type headache among musculoskeletal pain patients using regular analgesics.

OBJECTIVES: Tension-type headache (TTH) is the most prevalent type of primary headache disorder. Its acute pharmacotherapy is acetaminophen or non-steroidal anti-inflammatory drugs based on the Japanese Clinical Practice Guideline for Headache Disorders 2021. With Japan's aging population, however, the number of TTH patients with comorbidities that have been treated by analgesics is increasing. Under this context, it is sometimes difficult to select an acute pharmacotherapy for TTH. Kakkonto, Japanese traditional herbal kampo medicine, is empirically used for TTH. We hypothesized that kakkonto has efficacy for TTH with painful comorbidities. MATERIALS AND METHODS: We prospectively collected 10 consecutive TTH patients who had already taken analgesics for comorbidities. We prescribed 2.5 g of kakkonto (TJ-1), and patients took it. A numerical rating scale for pain before and 2 hours after kakkonto intake was evaluated. RESULTS: Eight women and 2 men were included. The mean age was 71.0 ± 13.4 years old. Four patients had lower back pain, 2 had lumbar spinal stenosis, 2 had knee pain, 1 had neck pain, and 1 had shoulder myofasciitis. Celecoxib was used for 4 patients, acetaminophen for 3, loxoprofen for 2, and a combination of tramadol and acetaminophen for 1, as routinely used analgesics. The median numerical rating scale statistically improved from the median of 4 to that of 0. There were no side effects of kakkonto. CONCLUSION: Kakkonto showed efficacy as an acute medication for TTH with comorbidities that have been treated by analgesic.