Does metabolic syndrome influence the efficacy of mirabegron treatment in female patients with overactive bladder?

INTRODUCTION AND HYPOTHESIS: We aimed to determine whether the presence of metabolic syndrome (MS) affects the efficacy of mirabegron in treatment-naïve women with overactive bladder (OAB). METHODS: Women being treated with mirabegron 50 mg were allocated to MS and non-MS groups, and the efficacy of treatment of OAB was compared using the OAB symptom score (OABSS) and a 3-day voiding diary before and 12 weeks after starting treatment. The Wilcoxon signed-rank and Mann-Whitney U tests and multivariate logistic regression were used for statistical analyses, and a p-value < 0.05 was considered to represent statistical significance. RESULTS: Of the 197 patients who completed the trial, 43 (23.9%) had MS. After 12 weeks of mirabegron treatment, both the MS and non-MS groups showed significant improvements in OABSS score, the number of incontinence episodes/24 h, the number of micturition episodes/24 h, and the number of episodes of urgency/24 h. The factors associated with clinically important differences in OABSS were the presence of hyperglycemia (odds ratio 2.43, 95% confidence interval [CI] 1.05-5.60) and OABSS score at baseline (odds ratio 1.23, 95% CI 1.09-1.39). CONCLUSIONS: Mirabegron is effective in patients with and without MS, and comorbid hyperglycemia and severe OAB symptoms before treatment are predictors of the efficacy of mirabegron treatment.

Long-Term Safety, Tolerability, and Efficacy of a Transdermal Donepezil Patch in Patients with Severe Alzheimer's Disease.

BACKGROUND: Oral formulations are not suitable for demented patients with dysphagia, those refuse to take tablets, or those with drug compliance problem. However, only oral formulations of donepezil hydrochloride are approved for the treatment of severe Alzheimer's disease in Japan. OBJECTIVE: To evaluate the safety, tolerability, and efficacy of long-term application of a 55.0 mg transdermal donepezil patch switched from a 10 mg oral donepezil hydrochloride tablet, for the treatment of patients with severe Alzheimer's disease. METHODS: A 52-week, multicenter, open-label, uncontrolled (phase III) study (jRCT2080224612) was conducted in Japan between April 2019 and August 2021. A 10 mg donepezil hydrochloride tablet was administered once a day for four weeks; a 55.0 mg donepezil patch was then applied once a day for 52 weeks in patients with severe Alzheimer's disease. RESULTS: Of 64 patients received the patch, 45 completed the 52-week period. The overall discontinuation rate was 29.7% (19/64). Among the 19 patients discontinued, six patients 9.4% (6/64) discontinued due to adverse events. The incidence of adverse events at application sites was 67.2% (43/64), including application site erythema 29.7% (19/64), application site pruritus 25.0% (16/64), and contact dermatitis 20.3% (13/64). Adverse events were mild and did not increase with time, demonstrating a favorable safety profile. Cognitive function, measured using the Mini-Mental State Examination, was maintained for up to 24 weeks. CONCLUSIONS: Adverse events were considered manageable in a clinical setting. The long-term application of a 55.0 mg donepezil patch once a day was feasible treatment in patients with severe Alzheimer's disease.

Successful treatment with levothyroxine for idiopathic hypersomnia patients with subclinical hypothyroidism.

OBJECTIVE: Our objective was to discuss the effect of levothyroxine on excessive daytime sleepiness (EDS) and a prolonged nocturnal sleep at patients with idiopathic hypersomnia who presented with subclinical hypothyroidism. METHODS: We present two patients with hypersomnia who complained of EDS and a prolonged nocturnal sleep time. Sleep architecture and subjective daytime sleepiness were estimated by polysomnography (PSG) and Epworth Sleepiness Scale (ESS), respectively. Diagnoses were made using the International Classification of Sleep Disorders, 2nd Edition criteria for idiopathic hypersomnia with long sleep time. RESULTS: PSG demonstrated a short sleep latency, a prolonged total sleep time and normal proportions of all non-rapid eye movement (REM) and REM sleep stages. Nocturnal PSG excluded other causes of EDS. No medical, neurological and mental disorders were present. Their laboratory data indicated mildly elevated thyrotropin, despite free thyroxine (T4) and triiodothyronine (T3) estimates within their reference ranges, which is a characteristic of latent hypothyroidism. Levothyroxine (25 microg/day) was administrated orally. After treatment with levothyroxine for 8 weeks, the mean daily sleep times decreased. EDS was also improved, and a significant decrease in the ESS score was observed. Levothyroxine was effective for their hypersomnia and well tolerated. CONCLUSIONS: It should be noted that hypersomnia may be associated with subclinical hypothyroidism, although few abnormalities in physical and neurological examinations are present.