Long-term efficacy and safety of two doses of Norditropin® (somatropin) in Noonan syndrome: a 4-year randomized, double-blind, multicenter trial in Japanese patients.

This 4-year randomized, double-blind, multicenter trial (NCT01927861) investigated the long-term efficacy and safety of Norditropin® (NN-220; somatropin) in Japanese children with short stature due to Noonan syndrome. Pre-pubertal children with Noonan syndrome were randomized 1:1 to receive 0.033 mg/kg/day (n = 25, mean age 6.57 years) or 0.066 mg/kg/day (n = 26, mean age 6.06 years) GH. Height standard deviation score (SDS) change after 208 weeks from baseline was evaluated using an analysis of covariance model. Height SDS improved from -3.24 at baseline with a significantly greater increase (estimated mean [95% confidence interval]) with 0.066 vs. 0.033 mg/kg/day GH (1.84 [1.58; 2.10] vs. 0.85 [0.59; 1.12]; estimated mean difference 0.99 [0.62; 1.36]; p < 0.0001). The majority of treatment-emergent adverse events (TEAEs) were non-serious, mild and assessed as unlikely treatment-related. TEAE rates and frequencies of serious TEAEs were similar between groups. Three patients receiving 0.066 mg/kg/day were withdrawn; two due to TEAEs at days 1,041 and 1,289. Mean insulin-like growth factor-I SDS increased from -1.71 to -0.75 (0.033 mg/kg/day) and 0.57 (0.066 mg/kg/day) (statistically significant difference). In both groups, there were only minor glycosylated hemoglobin changes, similar oral glucose tolerance test insulin response increases and no clinically relevant changes in oral glucose tolerance test blood glucose, vital signs, electrocardiogram or transthoracic echocardiography. In conclusion, treatment with 0.033 and 0.066 mg/kg/day GH for 208 weeks improved height SDS in Japanese children with short stature due to Noonan syndrome with a significantly greater increase with 0.066 vs. 0.033 mg/kg/day GH and was well tolerated, with no new safety concerns.

Cross-Country Skiing Analysis and Ski Technique Detection by High-Precision Kinematic Global Navigation Satellite System.

Cross-country skiing (XCS) embraces a broad variety of techniques applied like a gear system according to external conditions, slope topography, and skier-related factors. The continuous detection of applied skiing techniques and cycle characteristics by application of unobtrusive sensor technology can provide useful information to enhance the quality of training and competition. (1) Background: We evaluated the possibility of using a high-precision kinematic global navigation satellite system (GNSS) to detect cross-country skiing classical style technique. (2) Methods: A world-class male XC skier was analyzed during a classical style 5.3-km time trial recorded with a high-precision kinematic GNSS attached to the skier's head. A video camera was mounted on the lumbar region of the skier to detect the type and number of cycles of each technique used during the entire time trial. Based on the GNSS trajectory, distinct patterns of head displacement (up-down head motion) for each classical technique (e.g., diagonal stride (DIA), double poling (DP), kick double poling (KDP), herringbone (HB), and downhill) were defined. The applied skiing technique, skiing duration, skiing distance, skiing speed, and cycle time within a technique and the number of cycles were visually analyzed using both the GNSS signal and the video data by independent persons. Distinct patterns for each technique were counted by two methods: Head displacement with course inclination and without course inclination (net up-down head motion). (3) Results: Within the time trial, 49.6% (6 min, 46 s) was DP, 18.7% (2 min, 33 s) DIA, 6.1% (50 s) KDP, 3.3% (27 s) HB, and 22.3% (3 min, 03 s) downhill with respect to total skiing time (13 min, 09 s). The %Match for both methods 1 and 2 (net head motion) was high: 99.2% and 102.4%, respectively, for DP; 101.7% and 95.9%, respectively, for DIA; 89.4% and 100.0%, respectively, for KDP; 86.0% and 96.5%, respectively, in HB; and 98.6% and 99.6%, respectively, in total. (4) Conclusions: Based on the results of our study, it is suggested that a high-precision kinematic GNSS can be applied for precise detection of the type of technique, and the number of cycles used, duration, skiing speed, skiing distance, and cycle time for each technique, during a classical style XCS race.

Recognition and Practice of Hypopituitarism After Traumatic Brain Injury and Subarachnoid Hemorrhage in Japan: A Survey.

INTRODUCTION: Individuals with traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH) are at a high risk of hypopituitarism, and should benefit from early diagnosis and management. However, data on awareness, attitudes, and practices of physicians treating hypopituitarism post-TBI/SAH are limited. The objectives of this study were to gain an understanding of the awareness of Japanese neurosurgeons and endocrinologists towards hypopituitarism post-TBI/SAH and the need for pituitary function assessments in these patients; and to assess the practices and perspectives of these specialists on screening patients with this condition. METHODS: An observational, cross-sectional study was performed that included a Web-based survey of practicing neurosurgeons managing ≥ 1 new patients with TBI/SAH per year or endocrinologists with ≥ 1 new patients per year with a history of TBI/SAH. RESULTS: Of the 316 respondents (201 neurosurgeons [male, 95.5%]; 115 endocrinologists [male, 77.4%]), 75.6% of neurosurgeons and 81.7% of endocrinologists were aware of the probable occurrence of hypopituitarism post-TBI/SAH, and 79% neurosurgeons and 93.8% endocrinologists considered pituitary function impairment after TBI/SAH to be either very important or important. Hypopituitarism after TBI/SAH was recognized as an important concern by both neurosurgeons (79%) and endocrinologists (93.8%). Although many respondents agreed that such patients remain undiagnosed and untreated, pituitary function assessment post-TBI/SAH has only been performed to a limited extent. The awareness that post-TBI/SAH hypopituitarism is often transient and can progress over several weeks or months was lower in neurosurgeons (46.8%) than in endocrinologists (66.1%). CONCLUSIONS: The level of awareness of hypopituitarism post-TBI/SAH was lower among Japanese neurosurgeons than among endocrinologists. Educational programs and detailed guidance for the diagnosis and treatment of hypopituitarism post-TBI/SAH are warranted.