Design and daytime performance of laser-induced fluorescence spectrum lidar for simultaneous detection of multiple components, dissolved organic matter, phycocyanin, and chlorophyll in river water.

In this work, we developed mobile laser-induced fluorescence spectrum (LIFS) lidar based on preliminary experiments on the excitation emission matrix of a water sample and a method for reducing solar background light using the synchronous detection technique. The combination of a UV short-pulse laser (355 nm, 6 ns) for fluorescence excitation with a 10-100 ns short-time synchronous detection using a gated image-intensified multi-channel CCD of the fluorescence made the LIFS lidar operation possible even in daytime. The LIFS lidar with this construction demonstrated the potential of natural river/lake water quality monitoring at the Tenryu River/Lake Suwa. Three main components in the fluorescence data of the water, dissolved organic matter, phycocyanin, and chlorophyll, were extracted by spectral analysis using the standard spectral functions of these components. Their concentrations were estimated by adapting experimentally calibrated data. Results of long-term field observations using our LIFS lidar from 2010 to 2012 show the necessity of simultaneous multi-component detection to understand the natural water environment.

Transdermal rotigotine in early stage Parkinson's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: We conducted a randomized, double-blind, placebo-controlled trial to determine the safety and efficacy of transdermal rotigotine at doses up to 16 mg/24 hours in patients with early stage Parkinson's disease (PD) in Japan. METHODS: Patients received once-daily rotigotine 2 to 16 mg/24 hours (mean dose, 12.8 mg/24 hours; n = 82) or placebo (n = 90) for 12 weeks. The primary endpoint was the change in Unified Parkinson's Disease Rating Scale (UPDRS) part II (activities of daily living) and part III (motor function) scores from baseline to the end of treatment. RESULTS: The mean (± standard deviation) changes in UPDRS part II and III scores were -8.4 ± 9.7 in the rotigotine group and -4.1 ± 8.2 in the placebo group and were significantly different (P = 0.002). More patients in the rotigotine group than in the placebo group had a ≥ 20% score reduction. No serious drug-related adverse events were reported. CONCLUSIONS: Rotigotine at doses up to 16 mg/24 hours was well tolerated and improved function in patients with early stage PD.

Daytime symptoms of restless legs syndrome--clinical characteristics and rotigotine effectiveness.

OBJECTIVE: To elucidate the prevalence and clinical characteristics of daytime restless legs syndrome (RLS) among patients with idiopathic RLS and investigate the effectiveness of rotigotine for daytime RLS. METHODS: In 256 enrolled RLS patients, we investigated factors associated with the presence of RLS symptoms throughout the day. We also assessed the duration of daytime RLS symptoms at hourly intervals, time of initial symptom onset during the day, and associations between duration of daytime and nighttime RLS symptoms. In addition, we compared changes in duration and frequency of RLS symptoms during daytime and nighttime after randomly assigning patients to a 13-week treatment with rotigotine, a dopamine agonist patch with 24-hour action, or placebo. RESULTS: Eighty-one (31.6%) patients had daytime RLS symptoms. Only the International Restless Legs Syndrome Study Group rating scale total score was significantly associated with the presence of daytime RLS symptoms (p < 0.01) on multiple logistic regression analysis. Daytime RLS symptom onset was at 6 a.m. in 44.4% of patients; symptom duration increased significantly toward nighttime. There was a significant positive association between duration of daytime and nighttime RLS symptoms (p < 0.0001) and a greater statistically significant reduction of daytime RLS symptom duration with rotigotine treatment than with placebo (p = 0.03). CONCLUSIONS: Daytime symptoms are frequent in patients with RLS and may be associated with increased severity of the disorder and prolonged nighttime RLS symptoms. Rotigotine could become an important treatment choice for daytime symptoms.

Transdermal rotigotine in advanced Parkinson's disease: a randomized, double-blind, placebo-controlled trial.

Rotigotine, a non-ergot dopamine receptor agonist, offers potential for continuous dopaminergic stimulation that could avoid the fluctuations observed with traditional treatments. We conducted a randomized, double-blind, placebo-controlled trial in Japanese patients with advanced Parkinson's disease (PD) to investigate the efficacy and safety of rotigotine. Inclusion criteria included the presence of motor complications, such as wearing off, on-off, delayed-on/no-on, any circumstances that could interfere with levodopa dose escalation because of side effects, or declining levodopa efficacy. The enrolled patients received once-daily applications of rotigotine transdermal patches or matched placebo patches. A total of 174 patients were randomly assigned to rotigotine (87 patients) or placebo (87 patients). The full analysis set included 172 patients (86 for the rotigotine group and 86 for the placebo group). The maximum maintenance dose of rotigotine was set at 16 mg/24 h. The changes in unified PD rating scale Part III scores from baseline to the end of the trial were -10.1 ± 9.0 (mean ± standard deviation) in the rotigotine group and -4.4 ± 7.4 in the placebo group (p < 0.001). There was a significantly greater reduction in the off-time (p = 0.014) in the rotigotine group. Rotigotine was well tolerated, with serious adverse events being reported in only three patients in each group. Rotigotine at doses of up to 16 mg/24 h is efficacious and safe in Japanese patients with advanced PD.

Rotigotine vs ropinirole in advanced stage Parkinson's disease: a double-blind study.

OBJECTIVE: To confirm the superiority of transdermal rotigotine up to 16 mg/24 h over placebo, and non-inferiority to ropinirole, in Japanese Parkinson's disease (PD) patients on concomitant levodopa therapy. METHODS: This trial was a randomized, double-blind, double-dummy, three-arm parallel group placebo- and ropinirole-controlled trial. Four-hundred and twenty PD patients whose motor symptoms were not well controlled by levodopa treatment were randomized 2:2:1 to receive rotigotine, ropinirole (up to 15 mg/day) or placebo during a 16-week treatment period followed by a 4-week taper period. The primary variable was change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON state) sum score from baseline to the end of the treatment period. RESULTS: The difference in the change in the UPDRS Part III (ON state) sum score from baseline to the end of treatment between rotigotine and placebo groups was -6.4 ± 1.2 (95% CI: -8.7 to -4.1; p < 0.001), indicating superiority of rotigotine over placebo. The difference between rotigotine and ropinirole groups was -1.4 ± 1.0 (95% CI: -3.2 to 0.5), below the non-inferiority margin, indicating the non-inferiority of rotigotine to ropinirole. Application site reaction was seen in 57.7% of the patients in the rotigotine group and in 18.6% in the ropinirole group (P < 0.001). No other safety issue was noted. CONCLUSIONS: Rotigotine was well tolerated at doses up to 16 mg/24 h and showed similar efficacy to ropinirole except that the application site reaction was much higher in the rotigotine group.

Efficacy, safety and risk of augmentation of rotigotine for treating restless legs syndrome.

The present study aimed to examine the long-term efficacy and safety of rotigotine treatment for restless legs syndrome (RLS), as well as the rate of clinically significant augmentation, in a 1-year open-label study of Japanese subjects. Japanese patients with RLS who had been treated with rotigotine or placebo in a double-blind trial were enrolled in a 1-year, open-label, uncontrolled extension study and treated with rotigotine at a dose of up to 3 mg/24 h after an 8-week titration phase. Outcomes included International Restless Legs Syndrome Study Group rating scale (IRLS scale), Pittsburgh Sleep Quality Index (PSQI), safety, and investigator-/expert panel-assessed augmentation (including Augmentation Severity Rating Scale). Overall, 185 patients entered the open-label study and 133 completed the study. IRLS and PSQI total scores improved throughout the 52-week treatment period (IRLS, from 23.2±5.1 to 7.8±7.6 and PSQI, from 8.0±3.1 to 5.0±2.9). Treatment-emergent adverse events were mild to moderate in severity, and included application site reactions (52.4%) and nausea (28.6%). Clinically significant augmentation occurred in five patients (2.7%). These results indicate a good long-term efficacy of rotigotine for treating RLS, with a relatively low risk of clinically significant augmentation.

Efficacy and safety of rotigotine in Japanese patients with restless legs syndrome: a phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group study.

OBJECTIVE: We aimed to ascertain the efficacy and safety of transdermal rotigotine (2 and 3mg/24h) in Japanese patients with restless legs syndrome (RLS). METHODS: In our double-blind placebo-controlled study, 284 Japanese patients with idiopathic RLS were randomly assigned to receive rotigotine 2mg/24h or 3mg/24h, or placebo, for 13 weeks. The primary endpoint was the change in International Restless Legs Syndrome Study Group rating scale (IRLS) total score. RESULTS: The placebo-subtracted decreases in IRLS total score for rotigotine 2 mg/24 h and 3 mg/24 h were -2.8±1.3 and -3.1±1.3, respectively, which were significant (P<0.05). The interaction between baseline Pittsburgh Sleep Quality Index (PSQI) and treatment group for the change in IRLS total score was significant, indicating greater improvements in IRLS total score in patients with severe insomnia. Overall, 80.0%, 86.2%, and 51.6% of patients in the rotigotine 2 mg/24 h, 3 mg/24 h, and placebo groups, respectively, experienced adverse events (AEs) including application site reactions in 42.1%, 50.0%, and 7.4% of patients, respectively. None of the AEs were severe. CONCLUSIONS: Our results showed that rotigotine was effective without major safety concerns at doses of up to 3 mg/24 h in Japanese patients with RLS.