Metronidazole gel (0.75%) in Japanese patients with rosacea: A randomized, vehicle-controlled, phase 3 study.

Topical metronidazole is not currently approved in Japan as a treatment for the indication of rosacea, although 0.75% metronidazole gel was authorized in 2014 for the management of cancerous skin ulcers. We conducted a randomized, double-blind, vehicle-controlled study to evaluate the efficacy and safety of 0.75% metronidazole gel in Japanese patients with inflammatory lesions (papules/pustules) and erythema associated with moderate to severe rosacea. Overall, 130 patients were randomly assigned to receive 0.75% metronidazole gel (n = 65) or vehicle (n = 65), and 120 patients completed 12 weeks of treatment. The primary efficacy outcome was the proportion of patients who achieved both of the following at week 12: an improvement of >50% in the number of inflammatory lesions (papules/pustules) and a positive change of at least one degree in erythema severity. This composite outcome was achieved by 72.3% of metronidazole-treated patients versus 36.9% of vehicle-treated patients, with the between-group difference demonstrating significant improvement with 0.75% metronidazole gel (p < 0.0001). All secondary efficacy endpoints (patients achieving a score of ≥3 for percent change in the number of inflammatory lesions at week 12; patients achieving a score of ≥3 for change in erythema severity at week 12; patients achieving an Investigator's Global Assessment score of 0 or 1 at week 12; percent change over time in the number of inflammatory lesions; change over time in erythema severity) also showed improvement in the 0.75% metronidazole gel group. The incidence of adverse events was higher with metronidazole (40.0%) than with vehicle (29.2%). Of these, treatment-related, treatment-emergent adverse events occurred in 9.2% and 6.2% in the metronidazole and the vehicle group, respectively, but there were no new safety concerns. Overall, the results of this study have confirmed the efficacy and safety of 0.75% metronidazole gel in Japanese patients with rosacea.

Topical glycopyrronium tosylate in Japanese patients with primary axillary hyperhidrosis: A randomized, double-blind, vehicle-controlled study.

Glycopyrronium tosylate cloth, an anticholinergic drug, has been approved for the topical treatment of primary axillary hyperhidrosis in the USA, but its effects in Japanese patients have not been previously investigated. This 4-week, randomized, double-blind, vehicle-controlled, multicenter study was conducted to evaluate the efficacy and safety of glycopyrronium tosylate cloth for primary axillary hyperhidrosis patients in Japan. Eligible patients, who were ≥9 years of age and had primary axillary hyperhidrosis ≥6 months, with gravimetrically-measured sweat production ≥50 mg/5 min, and Hyperhidrosis Disease Severity Scale ≥3 (moderate) were randomized 1:1:1 to once daily topical glycopyrronium tosylate 3.75%, 2.5%, or vehicle. Overall, 497 patients (163 in the glycopyrronium tosylate 3.75% group, 168 in the glycopyrronium tosylate 2.5% group, and 166 in the vehicle group, hereinafter in this order) were randomized. Statistically higher proportions of patients in the glycopyrronium tosylate groups achieved ≥2-point improvement in Hyperhidrosis Disease Severity Scale and ≥50% reduction in sweat production from baseline versus vehicle at week 4 (51.6%, 41.1%, and 16.4%, respectively; p < 0.001 in both cases). Higher responder rates in the glycopyrronium tosylate groups compared with the vehicle group occurred as early as week 1. The most common treatment-emergent adverse events in patients treated with glycopyrronium tosylate were photophobia, mydriasis, thirst, and dysuria. Most treatment-emergent adverse events were mild as determined by the investigators. The incidence of treatment-emergent adverse events leading to treatment modification was low in the three groups. The 4-week use of topical glycopyrronium tosylate improved the patient-reported outcome measure Hyperhidrosis Disease Severity Scale and objectively-evaluated sweat production with a favorable benefit/risk profile.

Association between insulin resistance, cardiovascular risk factors and overweight in Japanese schoolchildren.

OBJECTIVE: The aim of this study was to examine the association between insulin resistance, cardiovascular risk factors and overweight in Japanese schoolchildren. METHODS: A cross-sectional study was performed on 310 schoolchildren (155 boys and 155 girls) of the fifth grade and the eighth grade in a town in Nagano Prefecture, Japan. The survey was conducted on anthropometric, blood examinations, and by calculation of body mass index (BMI: body weight/body height(2)) and HOMA-IR (fasting insulin × fasting glucose/405). RESULTS: Hemoglobin A1c and fasting glucose were not associated with BMI, whereas fasting insulin and HOMA-IR were significantly higher in overweight children in comparison with the lowest quartile BMI group. In the overweight, the mean and standard deviation of HOMA-IR were 2.51 ± 1.01, and the prevalence of HOMA-IR ≧ 2.5 was 46.8%. Schoolchildren with HOMA-IR ≧ 2.5 had more several cardiovascular risk factors. CONCLUSIONS: Insulin resistance was observed in overweight Japanese children, though their hemoglobin A1c and fasting glucose were within the normal range. In addition, with higher BMI, the number of cardiovascular risk factors was increased. Weight management should be started in childhood.

A positive association between leptin and blood pressure of normal range in Japanese men.

The results of previous studies on the relationship between leptin and blood pressure are discordant. We investigated to what extent the serum leptin level was related to blood pressure independent of the degree of insulin resistance. The subjects were 1916 men aged 34-69 years whose mean body mass index (BMI) was 23.0 kg/m2. Blood pressure was regressed by leptin concentrations with adjustments for age, BMI, insulin resistance, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, physical activity, drinking habits and smoking status. Leptin was associated with diastolic blood pressure (DBP) (standardized beta: 0.092, p = 0.003), but not with systolic blood pressure (SBP) (standardized beta: 0.035, p = 0.25), although insulin resistance was positively associated with both SBP and DBP (standardized beta: 0.175 for SBP, p < 0.001 and 0.114 for DBP, p < 0.001) among all subjects. After subjects were divided into those with normal blood pressure (SBP <130 mmHg and DBP <85 mmHg) and those with higher blood pressure, leptin was positively and significantly associated with DBP (standardized beta: 0.106, p = 0.012) independent of the degree of insulin resistance, but not with SBP (standardized beta: 0.064, p = 0.13) among subjects in the normal blood pressure range. Among the subjects with higher blood pressure, however, neither the association of leptin with SBP nor that of leptin with DBP was statistically significant. These findings suggest that leptin may maintain and increase arterial tone, resulting in the elevation of DBP only within normal blood pressure range. It is also likely that leptin is a physiological mediator--or at least a marker--of some degree of DBP elevation in obesity.

Plasma fibrinogen levels and cardiovascular risk factors in Japanese schoolchildren.

BACKGROUND: Plasma fibrinogen level has been recognized as an independent risk factor for atherosclerosis and its thrombotic complications in adults. The present study aimed to clarify the association between plasma fibrinogen levels and cardiovascular risk factors in Japanese children. METHODS: A total of 294 schoolchildren (145 boys and 149 girls) aged 10-13 years in a town in Nagano Prefecture, Japan, were surveyed in 2000 for body mass index (BMI), plasma fibrinogen, serum C-reactive protein (CRP), serum total cholesterol, serum high-density lipoprotein (HDL) cholesterol, hemoglobin (Hb) A1c, and ratio of serum total cholesterol to serum HDL cholesterol (TCHR). RESULTS: The mean value and standard deviation of plasma fibrinogen level among the schoolchildren was 226.0+/-39.7 mg/dL for boys and 245.3+/-40.9 mg/dL for girls; significantly higher for girls. Among plasma fibrinogen tertiles, serum CRP tended to increase with plasma fibrinogen in both boys and girls. An increasing trend was also found in serum total cholesterol in boys, and in TCHR, HbA1c and BMI in girls. Multiple linear regression analysis revealed significant associations of plasma fibrinogen with serum CRP and HbA1c in both sexes, with TCHR in boys, and with BMI in girls. CONCLUSIONS: Plasma fibrinogen levels were associated with cardiovascular risk factors such as serum CRP, TCHR, HbA1c, and BMI in Japanese schoolchildren.

[An attempt to prevent lifestyle-related diseases of schoolchildren in collaboration with parents, schools and communities].

PURPOSE: The authors focused on preventing lifestyle-related diseases among schoolchildren on the basis of health surveys with blood examinations and questionnaires on lifestyle in collaboration with parents, YOGO teachers, and public health nurses. The present study purposed to evaluate this approach using the PRECEDE-PROCEED Model. METHOD: The authors inquired of schoolchildren's parents their awareness of their children's health through health surveys of their children. Additionally, changes in the role of YOGO teachers and public health nurses before and after our attempt were assessed. The significance and problems with our approach were then evaluated based on the PRECEDE-PROCEED Model. RESULTS: Based on the PRECEDE-PROCEED Model, it was clarified that, for prevention of lifestyle-related diseases among schoolchildren, health surveys with blood examinations and questionnaires on lifestyle increased parents' interest in their children's health. On the basis of the results of health examinations, the role of YOGO teachers changed from leading figure for general health education to supporters of health promotion for individuals, with provision of health education classes in schools for this purpose. The role of public health nurses also changed from providing health education at the request of schools to supporting families to improve their lifestyle, including that of their children. CONCLUSIONS: In collaboration with children's parents, YOGO teachers and public health nurses, the present approach to prevent lifestyle-related diseases of schoolchildren on the basis of health surveys has advantages for increasing interest in schoolchildren's health, and should be useful for health promotion.

Plasma fibrinogen and its association with cardiovascular risk factors in apparently healthy Japanese subjects.

Recent evidence has shown the association of increased plasma fibrinogen levels with subsequent coronary heart disease or stroke. Fibrinogen is an acute-phase inflammatory reactant as well as a clotting factor. The authors investigated an association between fibrinogen levels and cardiovascular risk factors in apparently healthy Japanese subjects, while considering C-reactive protein (CRP) levels, a marker of the inflammatory status. Plasma fibrinogen and serum CRP from 2 706 participants in an annual mass screening examination, held in Matsukawa, Nagano, Japan were measured. A total of 2 355 subjects (816 men and 1 539 women) were analyzed after excluding individuals with a history of diabetes mellitus, heart disease, or stroke. Plasma fibrinogen was strongly correlated with CRP levels. After adjusting the CRP levels, fibrinogen was positively associated with age, smoking status, total cholesterol, and hemoglobin A(1c) (HbA(1c)) in men, and with age, total cholesterol, and HbA(1c) in women. On the other hand, high-density lipoprotein (HDL) cholesterol was a strong negative correlate of fibrinogen in both genders. Fibrinogen levels also tended to be associated positively with body mass index in both genders and negatively with exercise habits in men. The present multiple regression analysis has shown that plasma fibrinogen levels are correlated with conventional cardiovascular risk factors even after adjusting for the CRP levels. Persons with cardiovascular risk factors tended to have higher fibrinogen levels, suggesting that all elevated plasma fibrinogen concentration in those with risk factors may further increase the risk of the development of atherothrombosis and subsequent cardiovascular disease through the blood coagulation system.