Triptans are recommended for early use in the treatment of migraine attacks; however, real-world medication-taking behaviors and their relationship with interictal burden remain insufficiently understood. This study investigated the association between triptan use patterns and interictal burden in patients with migraine. A web-based cross-sectional survey was conducted among 302 women aged 20–59 years with migraine. Interictal burden was assessed using the Migraine Interictal Burden Scale (MIBS-4), and participants were classified into high- and low-burden groups. Triptan use, including frequency, timing of administration during migraine attacks, and patterns of medication use, was evaluated. Triptan use days were lower than headache days in both groups, suggesting that triptans were not used for all headache episodes. No significant differences were observed between groups in the type of triptan used or the timing of administration. In contrast, medication-taking behaviors differed significantly between groups. The high-burden group more frequently exhibited underuse behaviors, such as delaying or avoiding medication, as well as overuse behaviors, including early or additional dosing driven by anxiety. Satisfaction with triptan treatment was higher in the low-burden group, whereas the use of preventive medications did not differ between groups. Multivariable logistic regression analysis identified the coexistence of underuse- and overuse-related behaviors and HIT-6 score as independent factors associated with high interictal burden. These findings suggest that medication-taking behaviors characterized by both underuse- and overuse-related tendencies are independently associated with interictal burden in migraine. Future studies should evaluate whether interventions targeting maladaptive medication-taking behaviors are associated with improvements in headache management and disease burden.

Objective: To describe amitriptyline treatment modifications during a supply-restriction period and evaluate changes in pain intensity in an exploratory analysis. Methods: This single-center retrospective study included adults prescribed amitriptyline for pain management between January and December 2022 who remained on treatment when prescribing restrictions began in April 2023. Discontinuation or switching was assessed through March 2024. The primary endpoint was the proportion of patients who discontinued amitriptyline or switched to another drug for any reason. Treatment modifications were classified as either documented shortage-related or attributable to other clinical reasons. Numerical Rating Scale (NRS) changes were explored among shortage-related cases with paired baseline and 8-week assessments. Results: Of 180 patients screened, 83 were included. During the observation period, 81 patients (97.6%) underwent treatment modification for any reason, and 52 of 83 (62.7%) had treatment modifications explicitly documented as shortage-related. The remaining 29 modifications were attributed to inadequate pain control and/or adverse events. Among the 52 shortage-related cases, paired NRS scores were available for 33 patients. Median NRS scores were 5 [interquartile range (IQR), 3–7] at baseline and 5 [IQR, 4–6] at 8 weeks, with no significant overall change (p = 0.21). Changes did not differ significantly between the discontinuation and switching groups (p = 0.48). All patients with paired NRS scores were treated in the Department of Anesthesiology. Conclusions: Documented shortage-related treatment modification occurred in approximately two-thirds of eligible patients. The NRS findings were exploratory and should be interpreted cautiously because of potential selection bias.

BACKGROUND: Acute kidney injury (AKI) is associated with progression to chronic kidney disease, initiation of dialysis, and a decline in quality of life. Although rising temperatures have been linked to an increased risk of AKI, evidence regarding this association among outpatients in Japan remains limited. This study evaluated the association between community-acquired AKI (CA-AKI) and temperature using prefecture-level aggregated data. METHODS: We used Health Weather, a database integrating Japanese claims data with meteorological information. Among 4,868,549 individuals, we calculated the daily incidence of CA-AKI across 47 prefectures from 2018 to 2019. Associations were evaluated using the Cochran–Armitage trend test. RESULTS: CA-AKI incidence significantly increased as daily mean temperatures rose (p = 0.003). CONCLUSIONS: CA-AKI in Japan is significantly associated with higher temperatures. Preventive strategies should be tailored to the climatic characteristics of each geographic area.

Mesenchymal stromal cell transplantation therapy has been widely studied in regenerative medicine for the treatment of various diseases. We previously developed a mitochondria-targeted drug delivery system, termed the MITO-Porter, which enables large-scale production of coenzyme Q₁₀ (CoQ₁₀)-encapsulated carriers. This study aimed to generate mitochondrial-activated amnion-derived mesenchymal stromal cells (AMSCs) by delivering CoQ₁₀ to mitochondria using the MITO-Porter system, with the potential to improve AMSC transplantation outcomes. We treated AMSCs with CoQ₁₀-encapsulated MITO-Porter and evaluated cellular uptake, co-localization with mitochondria, changes in mitochondrial respiratory capacity, and antioxidant capacity. CoQ₁₀-encapsulated MITO-Porter was internalized by AMSCs and co-localized with mitochondria. Treatment of AMSCs with CoQ₁₀-encapsulated MITO-Porter significantly increased the mitochondrial oxygen consumption rate and decreased superoxide levels. Mitochondrial delivery of CoQ₁₀ successfully enhanced the mitochondrial respiratory capacity and antioxidant ability of AMSCs. These mitochondrial-activated AMSCs, newly generated using the MITO-Porter system, represent a promising cell source for improving MSC-based transplantation therapy.

Zolpidem is a non-benzodiazepine hypnotic that acts on γ-aminobutyric acid (GABA) type A (GABA_A) receptors and is widely used to treat insomnia. Our previous studies demonstrated that inflammation induced by bacterial mimetics, such as lipopolysaccharide (LPS), prolongs zolpidem-induced loss of righting reflex (LORR) in mice, suggesting that systemic inflammatory states modulate GABAergic transmission. However, it remains unclear whether viral inflammation produces similar effects. In this study, we investigated the effect of polyinosinic:polycytidylic acid (poly(I:C)), a synthetic analog of viral double-stranded RNA, on the duration of zolpidem-induced LORR in mice. Poly(I:C) administration significantly prolonged zolpidem-induced LORR. However, this prolongation was attenuated by pretreatment with bicuculline, a GABA_A receptor antagonist, and by bumetanide, an inhibitor of Na⁺-K⁺-2Cl⁻ cotransporter isoform 1 (NKCC1). In addition, we examined the mRNA expression levels of GABA_A receptor subunits, NKCC1, and K⁺-Cl⁻ cotransporter isoform 2 (KCC2) in the hippocampi of poly(I:C)-treated mice. Poly(I:C) treatment did not significantly alter the mRNA expression of major GABA_A receptor subunits but increased Slc12a2 mRNA expression, which encodes NKCC1 in the hippocampus. Importantly, poly(I:C)-induced prolongation of LORR was attenuated by bumetanide, an NKCC1 inhibitor. In conclusion, these findings suggest that viral mimetic-induced inflammation prolongs zolpidem-induced LORR, possibly through alterations in intracellular chloride homeostasis.

Background: Pivalate-conjugated β-lactam antibiotics (PCAs) have been developed to enhance bioavailability by incorporating the pivoxil group into the β-lactam chemical structure. Although there are only case reports and observational studies limited to pediatric patients on PCA-associated hypocarnitinemia, no comparisons have been made across all age groups, and comprehensive data from larger-scale studies are limited. Therefore, we investigated the association between PCA use and the onset of hypocarnitinemia for all age groups by analyzing the Japanese Adverse Drug Event Report (JADER) database. Methods: We analyzed 2,226,010 adverse event cases from the JADER database between April 2004 and March 2024. To detect signals of hypocarnitinemia, we calculated the reporting odds ratio and 95% confidence interval. Results: Among the total reported cases of hypocarnitinemia, the highest number of occurrences (252 cases) and the signal of hypocarnitinemia were detected in PCAs, whereas no cases were observed for other β-lactam antibiotics (non-PCAs). Multiple logistic regression analysis revealed that the PCA use, age (< 10 years), and concomitant use of valproate were associated with the onset of hypocarnitinemia. Most patients with hypocarnitinemia were under 10 years of age. An evaluation based on consumption data analysis from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) open database suggested that antimicrobial consumption is highest among children under 10 years of age. Conclusions: Our findings suggest that the use of β-lactam antibiotics containing a pivoxil moiety is disproportionately associated with reports of hypocarnitinemia in the JADER database. These findings should be interpreted as hypothesis-generating.

The coronavirus disease 2019 (COVID-19) pandemic substantially altered the epidemiology of seasonal influenza and markedly reduced the utilization of anti-influenza agents. Although influenza activity resumed following the relaxation of public health interventions, it remains unclear whether the utilization patterns of anti-influenza agents returned to the pre-pandemic state or changed after the pandemic. Prescription volumes of anti-influenza agents were extracted from the National Database of Health Insurance Claims and Specific Health Checkups Open Data (NDB Open Data) for fiscal years (FY) 2019–2024. Oseltamivir, baloxavir, zanamivir, and laninamivir were evaluated. To compare temporal changes among antiviral agents, prescription volumes were normalized using FY2019 as the reference (index = 100). Utilization of all evaluated anti-influenza agents declined markedly during FY2020 and FY2021. However, the recovery patterns differed substantially among antiviral agents following the resumption of influenza activity. In FY2024, the prescription index reached 297.0 for baloxavir 20-mg tablets and 191.6 for oseltamivir capsules/tablets, whereas zanamivir remained at 57.2. Laninamivir recovered to nearly the pre-pandemic level. These findings indicate that post-pandemic drug utilization differed substantially among antiviral agents. In conclusion, utilization patterns of anti-influenza agents in Japan changed following the COVID-19 pandemic. The heterogeneous recovery observed among antiviral agents suggests that post-pandemic utilization patterns may have been influenced by drug-specific characteristics in addition to the resurgence of influenza activity.

Fiber-rich foods are commonly consumed as part of dietary management or self-care by patients receiving long-term cardiometabolic pharmacotherapy. However, their physicochemical interactions with marketed pharmaceutical products under simulated intestinal conditions remain insufficiently characterized. This study evaluated the in vitro adsorption behavior of selected orally administered cardiometabolic drugs in artificial intestinal fluid in the presence of basil seeds or wheat bran. Commercially available products containing calcium channel blockers, beta-blockers, statins, or angiotensin II receptor blocker-related drugs were crushed and dispersed in artificial intestinal fluid, followed by the addition of basil seeds or wheat bran. Residual drug concentrations were determined by HPLC, and adsorption profiles were analyzed using pseudo-first-order and pseudo-second-order kinetic models. The reduction in residual drug concentration depended on both the drug and the food material. In the presence of wheat bran, amlodipine and carvedilol showed marked decreases in residual concentration, with residual rates of 32.9% and 16.6%, respectively, after 3 h. Nifedipine and olmesartan medoxomil also showed decreased residual concentrations, whereas bisoprolol, rosuvastatin, atorvastatin, and azilsartan showed only limited changes. The pseudo-second-order model showed better overall agreement with the adsorption profiles of the selected drugs. These findings provide a basis for further biopharmaceutical evaluation of physicochemical interactions between fiber-rich food materials and orally administered cardiometabolic drugs.

Cyanidin-3-glucoside (C3G) is a major anthocyanin present in various berries and pigmented grains and has been reported to exhibit antioxidant and anti-inflammatory activities. In the present study, we examined the effects of C3G on inflammatory responses in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with particular attention to adipocyte protein 2 (aP2), a lipid-associated protein implicated in inflammation. Treatment with C3G at concentrations up to 50 μM did not affect cell viability in the presence or absence of LPS. Quantitative real-time PCR analysis demonstrated that C3G significantly suppressed LPS-induced expression of aP2, as well as the pro-inflammatory cytokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). Furthermore, luciferase reporter assays revealed that C3G inhibited LPS-induced aP2 promoter activity in a manner independent of the peroxisome proliferator-activated receptor response element (PPRE)-like site. These findings indicate that C3G attenuates macrophage inflammatory responses through the suppression of aP2 expression and pro-inflammatory cytokine production, suggesting a novel molecular basis for the anti-inflammatory action of C3G.

This study aimed to identify factors influencing medical consultation among patients with migraine and to explore pharmacists’ roles in promoting appropriate care through the use of pharmacist-provided patient referral forms and burden assessment tools. An internet-based survey was conducted among 400 women aged 20–59 years identified as having migraine using a screening tool. Respondents were classified into the doctor-visited group (those who had visited a medical institution at least once) and the non-doctor-visited group (those who had never visited a medical institution). The doctor-visited group showed significantly higher scores on headache-related burden measures, including the Headache Impact Test-6 (HIT-6) and the Migraine Interictal Burden Scale-4 (MIBS-4) (p < 0.05), and a higher prevalence of symptoms such as aura, photophobia, and osmophobia. Although some participants in the non-doctor-visited group had high HIT-6 and MIBS-4 scores, they tended to perceive their headaches as “mild” or “temporary,” suggesting an underestimation of their burden. Approximately 70% of participants in both groups expressed positive attitudes toward patient referral forms, indicating potential usefulness in reducing anxiety regarding medical consultation. Among respondents in the non-doctor-visited group with little interest in patient referral forms, approximately 80% used over-the-counter (OTC) medications, and some had high HIT-6 and MIBS-4 scores. These findings suggest the potential role of burden assessment tools and patient referral forms in supporting patients in considering appropriate medical consultation during pharmacist intervention at the time of OTC medication purchase.