Some long work or shift work schedules necessitate an elevated and prolonged level of vigilance and performance but often result in sleep deprivation (SD), fatigue and sleepiness, which may impair efficiency. This study investigated the effects of a slow‐release caffeine [(SRC) at the daily dose of 600 mg] on vigilance and cognitive performance during a 64 h continuous wakefulness period. Sixteen healthy males volunteered for this double‐blind, randomised, placebo controlled, two‐way crossover study. A total of 300‐mg SRC or placebo (PBO) was given twice a day at 21:00 and 9:00 h during the SD period. Vigilance was objectively assessed with continuous electroencephalogram (EEG), the multiple sleep latency tests (MSLT) and wrist actigraphy. Cognitive functions (information processing and working memory), selective and divided attention were determined with computerised tests from the AGARD‐NATO STRES Battery (Standardised Tests for Research with Environmental Stressors). Attention was also assessed with a symbol cancellation task and a Stroop’s test; alertness was appreciated from visual analogue scales (VAS). Tests were performed at the hypo (02:00–04:00 h, 14:00–16:00 h) and hypervigilance (10:00–12:00 h, 22:00–00:00 h) periods during SD. Central temperature was continuously measured and safety of treatment was assessed from repeated clinical examinations. Compared with PBO, MSLT showed that SRC subjects were more vigilant from the onset (P=0.001) to the end of SD (P < 0.0001) whereas some cognitive functions were improved till the thirty third of SD but others were ameliorated through all the SD period and alertness was better from the thirteenth hour of SD, as shown by Stroop’s test (P=0.048). We showed that 300‐mg SRC given twice daily during a 64‐h SD is able to antagonize the impairment produced on vigilance and cognitive functions.

BACKGROUND Nomegestrol acetate/17β-estradiol (NOMAC/E(2)) is a new monophasic oral contraceptive combining NOMAC (2.5 mg), a highly selective progesterone-derived progestogen, with E(2) (1.5 mg), which is structurally identical to endogenous estrogen. The objective of this study was to compare the effects on ovarian activity of two different NOMAC/E(2) regimens. METHODS This was a double-blind, randomized study. Healthy, premenopausal women (aged 18-38 years, previous menstrual cycle length 28 ± 7 days) were randomized by computer-generated code to once-daily NOMAC/E(2) for three consecutive 28-day cycles: either 24 days with a 4-day placebo interval (n = 40) or 21 days with a 7-day placebo interval (n = 37) per cycle. Follicular growth (primary outcome measure), plasma hormone profiles and bleeding patterns were assessed. RESULTS There was no evidence of ovulation during treatment with either NOMAC/E(2) regimen. The largest follicle diameter was significantly smaller in the 24-day group than in the 21-day group [mean (SD) mm in cycle 2: 9.0 (3.0) versus 11.3 (5.3) (P = 0.02); in cycle 3: 9.2 (3.0) versus 11.5 (6.0) (P = 0.04)]. Mean FSH plasma levels were significantly lower in the 24-day versus the 21-day group on Day 24 of cycles 1 and 2. Withdrawal bleeding duration was significantly shorter in the 24-day than in the 21-day group [mean (SD) days after cycle 1: 3.5 (1.3) versus 5.0 (2.6) (P = 0.002); after cycle 2: 3.9 (1.6) versus 4.8 (1.7) (P = 0.03)]. CONCLUSIONS The 24-day NOMAC/E(2) regimen was associated with greater inhibition of follicular growth and shorter duration of withdrawal bleeding than the 21-day regimen, suggesting the shorter pill-free interval results in a greater margin of contraceptive efficacy and tolerability, and fewer withdrawal symptoms.

. It is found in coffee, of course, but also in tea, chocolate-flavored products and cola-based beverages, etc. 1 Due to its behavioral and psychomotor stimulating properties, it is used to maintain vigilance, memory, and performance levels during limited sleep deprivation. [2][3][4][5][6][7][8] Some prolonged sleep deprivation and wake-sleep rhythm disruptions are common in everyday life, especially in emergency cases, during rescue operations, in the army, or during transmeridian flights. These situations lead to a certain number of vigilance and performance alterations, which in turn lead to a decrease in efficacy or to the onset of penalizing symptomatology. [9][10][11][12] However, the results obtained with the use of caffeine to increase vigilance and performance level vary greatly. Sometimes, the results are very positive; an increase in performance mainly in visual vigilance tasks 13 can be observed as well as an increase in the level of awakeness-measured by electrophysiological techniques 2 -for unusual situations such as night work. Other studies reported an absence of effects or heterogeneous results 14 and sometimes negative effects such as the onset of tolerance during repeated intake of caffeine 15 or the onset of anxiety with still relatively low doses (325 mg). 16 In a general way, all the studies selected from a bibliographic research report an unquestionable stimulating and awaking effect of caffeine, but the effect has a limited power-especially compared with amphetamine-and duration. 17,18 Moreover, repeated caffeine intake can lead to the onset of deleterious cardiovascular or neurological side effects when the dose exceeds 600 mg. Therefore, it seemed interesting to assess the effects of a new galenic form of caffeine called " slowrelease " caffeine (SR caffeine) Stinergic. The release of Study Objectives: The aim of this study is to assess the interest of the intake of a new galenic form of caffeine called " slowrelease " caffeine (SR caffeine) during a decrease of vigilance due to a limited sleep deprivation. Design: The controlled method used compared three doses of SR caffeine (150, 300 and 600 mg) with a placebo. Tests were performed 2, 9 and 13 hours after each treatment. Wakefulness level was assessed subjectively through questionnaires and analog visual scales, and objectively with the Multiple Sleep Latency Test. Performance level was also assessed regularly with an attention test, a grammatical reasoning test, a spatial recognition test, a mathematical processing test, a visual tracking test, a memory search test, and a dual task. The motor activity was evaluated by wrist actimeter and safety of treatment was observed by regular clinical examination. Setting: NA Participants: Twenty-four young and healthy volunteers (12 men and 12 women) participated in a 32-hour sleep deprivation. Interventions: NA Results: The results show a significant effect of slow-release caffeine vs. placebo, and on vigilance and performance when subjects became tired. The effects of SR caffeine lasted 13...

Objective To investigate the clinical effect of SR49059 when given shortly before the onset of menstruDesign A double-blind, randomised, placebo-controlled, cross-over trial in complete block design (three Setting A clinical research organisation in Paris, France.Participants Women aged 18-35 years suffering from primary dysmenorrhoea. InterventionsIn each of three menstrual cycles, women reported to the study centre and were given a daily dose of either placebo, 100 mg or 300 mg SR49059 from a minimum of 4 hours up to a maximum of three days before the onset of bleeding and/or menstrual pain. If this did not control the pain, women were allowed once a day to take a second dose of study treatment providing that at least 4 hours had passed since the first drug intake.Main outcome measures Intensity of menstrual pain recorded by means of a visual analogue scale. Rating of symptoms of dysmenorrhoea (mainly back and pelvic pain) in relation to functional capacity (Sultan score). Self-assessment of menstrual blood loss in a menstrual diary record.Results Analysis of intensity of menstrual pain, as recorded by visual analogue scale and Sultan pain score (back and pelvic pain) during the first 24 hours of dysmenorrhoea, showed a dose-related effect of SR49059. The 300 mg dose of SR49059 was significantly more effective than placebo. Similarly, a dose-related effect of SR49059 was shown on total Sultan score. SR49059 was well tolerated and no significant effect on the bleeding pattern was noted.Conclusions This study showed for the first time a therapeutic effect of an orally active vasopressin V,, receptor antagonist in the prevention of dysmenorrhoea. Further studies are required to examine effect mechanisms and determine effective doses.ation as a preventative treatment of dysmenorrhoea.periods, three treatments).

Aim: We aimed to evaluate the gastro-intestinal tolerance to an indigestible bulking sweetener containing sugar alcohol using a double-blind random cross-over study. Method: In order to simulate their usual pattern of consumption, 12 healthy volunteers ingested maltitol or sucrose throughout the day, either occasionally (once a week for each sugar, first period) or regularly (every day for two 9 day periods, second period). In both patterns of consumption, daily sugar doses were increased until diarrhea and=or a grade 3 (ie severe) digestive symptom occurred, at which the dose level was defined as the threshold dose (TD). Results: In the first period (occasional consumption), the mean TD was 92 AE 6 g with maltitol and 106 AE 4 g with sucrose (P ¼ 0.059). The mean intensity of digestive symptoms was 1.1 and 1.3, respectively (P ¼ NS). Diarrhea appeared in six and one subjects respectively (P ¼ 0.035). In the second period (regular consumption), the mean TD was 93 AE 9 g with maltitol and 113 AE 7 g with sucrose (P ¼ 0.008). The mean intensity of digestive symptoms was 1.7 and 1.2, respectively (P ¼ NS). However, diarrhea appeared in eight and three subjects, respectively (P ¼ 0.04). Maltitol and sucrose TDs between the two periods were not different. Conclusions: Under our experimental conditions, in comparison to sucrose: (a) occasional or regular consumption of maltitol is not associated with severe digestive symptoms; (b) in both patterns of maltitol consumption, diarrhea frequency is higher, but it appeared only for very high doses of maltitol, much greater than those currently used; (c) maltitol does not lead to intestinal flora adaptation after a 9 day period of consumption.