This study investigated the effect of bergamot essential oil (BEO) or linalool, a major volatile component of BEO, on the nociceptive response to formalin. Plantar subcutaneous injection of BEO or linalool into the ipsilateral hindpaw reduced both the first and late phases of the formalininduced licking and biting responses in mice. Plantar subcutaneous injection of BEO or linalool into the contralateral hindpaw did not yield an antinociceptive effect, suggesting that the antinociceptive effect of BEO or linalool in the formalin test occurred peripherally. Intraperitoneal and plantar subcutaneous injection pretreatment with naloxone hydrochloride, an opioid receptor antagonist, significantly attenuated both BEO-and linalool-induced antinociception. Pretreatment with naloxone methiodide, a peripherally acting opioid receptor antagonists, also significantly antagonized the antinociceptive effects of BEO and linalool. Our results provide evidence for the involvement of peripheral opioids in antinociception induced by BEO and linalool. These results suggest that activation of peripheral opioid receptors may play an important role in reducing formalin-induced nociception.The essential oil of bergamot (BEO; Citrus bergamia Risso) is one of the most commonly used essential oils and is familiar to most of the general public. BEO is obtained by cold pressing of the epicarp and part of the mesocarp of the fresh bergamot fruit. BEO consists of a volatile (93-96%) and a nonvolatile fraction (4-7%); the former contains monoterpene and sesquiterpene hydrocarbons and oxygenated derivatives such as linalool and linalyl acetate, while the latter fraction contains waxes, polymethoxylated flavones, coumarins, and psoralens such as bergamottin and bergapten (6,14). BEO has been reported to minimize symptoms of stress-induced anxiety and mild mood disorders, as well as cancer pain, however the mechanistic basis for its use in such applications awaits discovery (1). A previous in vitro study showed that BEO reduced neuronal damage caused by excitotoxic stimuli (5), and significantly increased the extracellular levels of the inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) in rat hippocampus (15). Linalool is a monoterpene compound and is the main volatile component of the essential oils of various plants, including BEO. It has previously been reported that linalool administration produced antibacterial, anticonvulsant, and anti-inflammatory effects, as well as showing antinociceptive activity in several behavioral assays (2)(3)(4)(16)(17)(18)(19)(20). Furthermore, linalool can significantly reduce both mor-

What is known and objective Augmented renal clearance (ARC; hyperfiltration with over 130 mL/min/1.73 m2 of creatinine clearance (CLcr)) commonly occurs in critically ill patients. Recent reports indicate that ARC also occurs in haematologic malignancies. However, the risk factors for ARC in haematologic malignancies remain unknown, and there is no established method to predict ARC in haematologic malignancies. Our objective was to explore the risk factors for ARC retrospectively and develop a scoring method to predict ARC. Methods A single‐centre, retrospective, observational cohort study was conducted at the Sendai Medical Center (Sendai, Japan); 133 patients (April 2017‐March 2019) and 41 patients (April‐November 2019) with haematopoietic tumours who were administered vancomycin were enrolled in the analysis and validation cohorts, respectively. To define ARC, we calculated the vancomycin serum concentration when CLcr = 130 mL/min/1.73 m2 using a one‐compartment model. Patients with ARC were defined as those whose actual concentration of vancomycin remained lower than the calculated concentration. Using the analysis cohort, we explored risk factors of ARC and developed a scoring method to predict ARC in haematologic malignancies. The reproducibility of the scoring system was demonstrated using the validation cohort. Results and discussion Through multivariate analysis, young age (P < .001), leukaemia (P = .001) and low serum creatinine (P < .001) were identified as risk factors. According to this result, we established the ARC detection method: age ≤ 50 years = 3 points, 50 years < age ≤65 years = 1 point, leukaemia = 2 points, low SCr = 2 points; patients scoring ≥ 5 points represent the ARC high‐risk group. Using this scoring system, we could detect ARC with a sensitivity and specificity of 60.0% and 89.7% in the analysis cohort and 90.0% and 90.9% in the validation cohort, respectively. What is new and conclusion Our scoring method could predict ARC in haematologic malignancies and is useful as a simple screening tool for ARC.

Background Tenofovir disoproxil fumarate (TDF) has a strong antiviral effect, but TDF is known to cause renal dysfunction. Therefore, we are investigating preventing renal dysfunction by replacing TDF with tenofovir alafenamide fumarate (TAF), which is known to be relatively safe to the kidneys. However, the changes in renal function under long-term use of TAF are not known. In this study, we evaluated renal function in Japanese HIV-1-positive patients switching to TAF after long-term treatment with TDF. Methods A single-center observational study was conducted in Japanese HIV-1-positive patients. TDF was switched to TAF after at least 48 weeks of the treatment so we could evaluate the long-term use of TDF. The primary endpoint was the estimated glomerular filtration rate (eGFR) at 144 weeks of TAF administration. In addition, we predicted the factors that would lead to changes in eGFR after long-term use of TAF. Results Of the 125 HIV-1-positive patients who were prescribed TAF at our hospital during the study period, 70 fulfilled the study criteria. The eGFR at the time of switching from TDF to TAF was 81.4 ± 21.1 mL/min/1.73 m2. eGFR improved significantly after 12 weeks of taking TAF but significantly decreased at 96 and 144 weeks. The factors significantly correlated with the decrease in eGFR at 144 weeks on TAF were eGFR and weight at the start of TAF. Conclusions In this study, it was confirmed that switching to TAF was effective for Japanese HIV-1-positive patients who had been taking TDF for a long period of time and had a reduced eGFR. It was also found that the transition status depended on the eGFR and weight at the time of switch. Since HIV-1-positive patients in Japan are expected to continue taking TAF for a long time, renal function and body weight should be carefully monitored.