Meta-analysis: proton-pump inhibition in high-risk patients with acute peptic ulcer bleeding.

BACKGROUND: Recent data suggest that profound acid suppression may improve outcomes of patients in peptic ulcer bleeding. AIM: To better characterize the role of different pharmacological therapies in this population. METHODS: MEDLINE was used to identify randomized trials (01/1990-04/2003) that assessed the efficacy of pharmacological treatments for patients with bleeding peptic ulcers exhibiting high-risk stigmata (Forrest Ia-IIb). Three groups of treatment were assessed: proton-pump inhibitors given as high-dose bolus followed by intravenous constant infusion (40-80 mg and at least 6 mg/h), high-dose oral proton-pump inhibitors (at least twice the standard dosage), non-high-dose proton-pump inhibitors (other proton-pump inhibitors dosing schedules). Mixed-effect models were used to determine rate differences between treatment and control groups. RESULTS: Eighteen studies (1855 patients) were included. High-dose intravenous proton-pump inhibitors significantly reduced rebleeding (-14.6%), surgery (-5.4%) and mortality (-2.7%) compared with placebo, and rebleeding (-20.6%) compared with H(2)RA. Compared with placebo, high-dose oral proton-pump inhibitors significantly reduced only rebleeding (-11.8%), while non-high-dose proton-pump inhibitor treatment significantly improved all three outcomes. CONCLUSIONS: High-dose intravenous proton-pump inhibitor significantly decreases ulcer rebleeding, surgery and mortality. Early data on high-dose oral proton-pump inhibitor suggest improved rebleeding. The non-high-dose proton-pump inhibitor regimens, including a broad range of dosing, also improved outcomes, suggesting that doses inferior to those in the high-dose intravenous proton-pump inhibitor may be effective.

Profile of 24-h light exposure and circadian phase of melatonin secretion in night workers.

Light exposure was measured in 30 permanent night nurses to determine if specific light/dark profiles could be associated with a better circadian adaptation. Circadian adaptation was defined as a significant shift in the timing of the episode of melatonin secretion into the daytime. Light exposure was continuously recorded with ambulatory wrist monitors for 56 h, including 3 consecutive nights of work. Participants were then admitted to the laboratory for 24 h where urine was collected every 2 h under dim light for the determination of 6-sulphatoxymelatonin concentration. Cosinor analysis was used to estimate the phase position of the episode of melatonin secretion. Five participants showed a circadian adaptation by phase delay ("delayed participants") and 3 participants showed a circadian adaptation by phase advance ("advanced participants"). The other 22 participants had a timing of melatonin secretion typical of day-oriented people ("nonshifters"). There was no significant difference between the 3 groups for total light exposure or for bright light exposure in the morning when traveling home. However, the 24-h profiles of light exposure were very distinctive. The timing of the main sleep episode was associated with the timing of light exposure. Delayed participants, however, slept in darker bedrooms, and this had a major impact on their profile of light/dark exposure. Delayed and advanced participants scored as evening and morning types, respectively, on a morningness-eveningness scale. This observation suggests that circadian phase prior to night work may contribute to the initial step toward circadian adaptation, later reinforced by specific patterns of light exposure.

Association between melatonin secretion and daytime sleep complaints in night nurses.

STUDY OBJECTIVES: To test the hypothesis that nightworkers' diurnal sleep complaints are associated with the timing of melatonin secretion. DESIGN: After a minimum of three consecutive night shifts, the subjects were admitted to the laboratory for 24 hours during which they were allowed to eat and sleep ad lib. Urine was collected every two hours under dim illumination (<25 lux). Concentration of urinary 6-sulphatoxymelatonin (UaMT6s) was determined by radioimmunoassay. Sleep quality was assessed by questionnaires. SETTING: NA PARTICIPANTS: Two groups of 15 night nurses with mild and severe daytime sleep complaints. INTERVENTIONS: NA RESULTS: The proportion of the episode of UaMT6s excretion happening during the day (between 08:00 and 00:00 hours) was smaller in the group of nightworkers with severe daytime sleep complaints, and was negatively correlated with the severity of the complaints over the 30 subjects. A longer duration of melatonin secretion was associated with a lower severity of daytime sleep complaints. However, in most of the subjects with good daytime sleep quality, melatonin secretion remained essentially nocturnal, and the overlap with the time of their sleep episode was small or even absent. CONCLUSIONS: Timing and duration of melatonin secretion were associated with better daytime sleep quality when the subjects had an increased proportion of melatonin secreted during the day. When there was an indication of circadian phase shift, the direction of the shift was not of primary importance for daytime sleep quality. A longer duration of melatonin secretion may increase the tolerance to an abnormal circadian phase.