Study protocol for efficacy and safety of steroid-containing mouthwash to prevent chemotherapy-induced stomatitis in women with breast cancer: a multicentre, open-label, randomised phase 2 study

INTRODUCTION: Stomatitis is a frequent adverse event in patients undergoing chemotherapy for breast cancer. Stomatitis can hamper oral nutrition resulting in malnutrition, reduce quality of life and introduce the need for dose reductions and interruption of chemotherapy; however, there is currently no standard approach for preventing chemotherapy-induced stomatitis. We aimed to assess the safety and efficacy of a dexamethasone-based elixir mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer. METHODS AND ANALYSIS: In this multicenter, randomised, controlled phase 2 trial, we will randomly assign 120 women with early breast cancer undergoing chemotherapy to use of a dexamethasone-based elixir or standard oral care, to compare their preventive effects on chemotherapy-induced stomatitis. Patients will be assigned in a 1:1 ratio. Patients in the intervention group will receive chemotherapy, oral care and a dexamethasone-based elixir (10?mL 0.1?mg/mL; swish for 2?min and spit, four times daily for 9 weeks), and patients in the control group will receive chemotherapy and oral care. The primary endpoint is the difference in incidence of stomatitis between the two groups. The sample size allows for the detection of a minimum difference of 20% in the incidence of stomatitis between the two groups. Secondary endpoints are severity of stomatitis, duration of stomatitis, completion rate of chemotherapy and adverse events. ETHICS AND DISSEMINATION: All participants signed a written consent form, and the study protocol has been reviewed and approved by the Clinical Research Review Board of Nagasaki University (CRB7180001). TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000030489)

Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice

金沢大学医薬保健研究域医学系Oxytocin sets the stage for childbirth by initiating uterine contractions, lactation and maternal bonding behaviours. Mice lacking secreted oxcytocin (Oxt -/-, Cd38 -/-) or its receptor (Oxtr -/-) fail to nurture. Normal maternal behaviour is restored by peripheral oxcytocin replacement in Oxt -/- and Cd38 -/-, but not Oxtr -/- mice, implying that circulating oxcytocin crosses the blood-brain barrier. Exogenous oxcytocin also has behavioural effects in humans. However, circulating polypeptides are typically excluded from the brain. We show that oxcytocin is transported into the brain by receptor for advanced glycation end-products (RAGE) on brain capillary endothelial cells. The increases in oxcytocin in the brain which follow exogenous administration are lost in Ager -/- male mice lacking RAGE, and behaviours characteristic to abnormalities in oxcytocin signalling are recapitulated in Ager -/- mice, including deficits in maternal bonding and hyperactivity. Our findings show that RAGE-mediated transport is critical to the behavioural actions of oxcytocin associated with parenting and social bonding.3082047

Clinical Implications of the Change in Glomerular Filtration Rate with Adrenergic Blockers in Patients with Morning Hypertension: The Japan Morning Surge-1 Study

Background. The aim of this study was to clarify the relationship between the change in estimated glomerular filtration rate (eGFR) and urinary albumin by antihypertensive treatment. Methods. We randomized 611 treated patients with morning hypertension into either an added treatment group, for whom doxazosin was added to the current medication, or a control group, who continued their current medications. We compared the change in eGFR and urinary albumin creatinine ratio (UACR) between the groups. Results. The extent of the reduction in eGFR was significantly greater in the added treatment group than in the control group (−3.83  versus −1.08 mL/min/1.73 m2, P=0.001). In multivariable analyses, the change in eGFR was positively associated with the change in UACR in the added treatment group (β=0.20, P=0.001), but not in the control group (β=−0.002, P=0.97). When the changes in eGFR were divided by each CKD stage, eGFR was significantly more decreased in stage 1 than in the other stages in the added treatment group (P<0.001), but no differences were seen in the control group (P=0.44). Conclusion. The reduction of eGFR could be seen only in the early stage of CKD, and this treatment appeared to have no negative effect on renal function

Clinical Implications of the Change in Glomerular Filtration Rate with Adrenergic Blockers in Patients with Morning Hypertension: The Japan Morning Surge-1 Study

Background. The aim of this study was to clarify the relationship between the change in estimated glomerular filtration rate (eGFR) and urinary albumin by antihypertensive treatment. Methods. We randomized 611 treated patients with morning hypertension into either an added treatment group, for whom doxazosin was added to the current medication, or a control group, who continued their current medications. We compared the change in eGFR and urinary albumin creatinine ratio (UACR) between the groups. Results. The extent of the reduction in eGFR was significantly greater in the added treatment group than in the control group (−3.83  versus −1.08 mL/min/1.73 m2, P=0.001). In multivariable analyses, the change in eGFR was positively associated with the change in UACR in the added treatment group (β=0.20, P=0.001), but not in the control group (β=−0.002, P=0.97). When the changes in eGFR were divided by each CKD stage, eGFR was significantly more decreased in stage 1 than in the other stages in the added treatment group (P<0.001), but no differences were seen in the control group (P=0.44). Conclusion. The reduction of eGFR could be seen only in the early stage of CKD, and this treatment appeared to have no negative effect on renal function