Combined caffeine and bright light reduces dangerous driving in sleep-deprived healthy volunteers: a pilot cross-over randomised controlled trial.

AIM OF THE STUDY: To explore the effects of caffeine and bright light therapy on simulated nighttime driving in sleep-deprived healthy volunteers. PARTICIPANTS AND METHODS: Twelve male healthy volunteers aged 20 to 50 years participated in a randomized cross-over study of simulated nighttime driving at a sleep laboratory, followed by recovery sleep with polysomnography at home. The volunteers received variable combinations of caffeine 200mg (C+), caffeine placebo (C-), bright light 10,000 lux (L+), and bright light placebo<50 lux (L-), in four sessions (C+L+, C+L-, C-L+, C-L-), in random order with a wash-out period of 7 days. Treatments were given at 1 a.m. and testing was performed at 1:30 a.m., 3 a.m., 4 a.m., and 6 a.m. Lane drifting was the primary outcome measure. Other measures were reaction times, self-rated fatigue, sleepiness and recovery sleep. RESULTS: Without treatment, lane drifting increased throughout the night, and objective and subjective vigilance declined. Paired comparisons showed that lane drifting was significantly worse at 6 a.m. and at 4 a.m. than at 1:30 a.m. There was a global treatment effect on lane drifting. Lane drifting at 6 a.m. was significantly decreased with C+L+ compared to C-L-. CONCLUSIONS: Bright light therapy combined with caffeine administered at 1 a.m. decreased lane drifting by healthy volunteers during simulated nighttime driving.

Circadian rhythms, melatonin and depression.

The master biological clock situated in the suprachiasmatic nuclei of the anterior hypothalamus plays a vital role in orchestrating the circadian rhythms of multiple biological processes. Increasing evidence points to a role of the biological clock in the development of depression. In seasonal depression and in bipolar disorders it seems likely that the circadian system plays a vital role in the genesis of the disorder. For major unipolar depressive disorder (MDD) available data suggest a primary involvement of the circadian system but further and larger studies are necessary to conclude. Melatonin and melatonin agonists have chronobiotic effects, which mean that they can readjust the circadian system. Seasonal affective disorders and mood disturbances caused by circadian malfunction are theoretically treatable by manipulating the circadian system using chronobiotic drugs, chronotherapy or bright light therapy. In MDD, melatonin alone has no antidepressant action but novel melatoninergic compounds demonstrate antidepressant properties. Of these, the most advanced is the novel melatonin agonist agomelatine, which combines joint MT1 and MT2 agonism with 5-HT(2C) receptor antagonism. Adding a chronobiotic effect to the inhibition of 5-HT(2C) receptors may explain the rapid impact of agomelatine on depression, since studies showed that agomelatine had an early impact on sleep quality and alertness at awakening. Further studies are necessary in order to better characterize the effect of agomelatine and other novel melatoninergic drugs on the circadian system of MDD patients. In summary, antidepressants with intrinsic chronobiotic properties offer a novel approach to treatment of depression.

Chest physiotherapy in cystic fibrosis: improved tolerance with nasal pressure support ventilation.

OBJECTIVE: Chest physiotherapy (CPT) is an integral part of the treatment of patients with cystic fibrosis (CF). CPT imposes additional respiratory work that may carry a risk of respiratory muscle fatigue. Inspiratory pressure support ventilation (PSV) is a new mode of ventilatory assistance designed to maintain a constant preset positive airway pressure during spontaneous inspiration with the goal of decreasing the patient's inspiratory work. The aim of our study was 1) to evaluate respiratory muscle fatigue and oxygen desaturation during CPT and 2) to determine whether noninvasive PSV can relieve these potential adverse effects of CPT. METHODS: Sixteen CF patients in stable condition with a mean age of 13 +/- 4 years participated to the study. For CPT, we used the forced expiratory technique (FET), which consisted of one or more slow active expirations starting near the total lung capacity (TLC) and ending near the residual volume. After each expiration, the child was asked to perform a slow, nonmaximal, diaphragmatic inspiration. After one to four forced breathing cycles, the child was asked to cough and to expectorate. A typical 20-minute CPT session consisted of 10 to 15 FET maneuvers separated by rest periods of 10 to 20 breathing cycles each. During the study, each patient received two CPT sessions in random order on two different days, at the same time of day, with the same physiotherapist. During one of these two sessions, PSV was provided throughout the session (PSV session) via a nasal mask using the pressure support generator ARM25 designed for acute patients (TAEMA, Antony, France). The control session was performed with no nasal mask or PSV. Both CPT sessions were performed without supplemental oxygen. Lung function and maximal inspiratory pressures (PImax) and expiratory pressures (PEmax) were recorded before and after each CPT session. RESULTS: Mean lung function parameters were comparable before the PSV and the control sessions. Baseline pulse oximetry (SpO2) was significantly correlated with the baseline vital capacity (% predicted) and forced expiratory volume in 1 second (FEV1) (% predicted). PSV was associated with an increase in tidal volume (Vt) from 0.42 +/- 0.01 liters to 1.0 +/- 0.02 liters. Respiratory rate was significantly lower during PSV. SpO2 between the FET maneuvers was significantly higher during PSV as compared with the control session. SpO2 decreases after FET were significantly larger during the control session (nadir: 91.8 +/- 0. 7%) than during the PSV session (93.8 +/- 0.6%). Maximal pressures decreased during the control session (from 71.9 +/- 6.1 to 60.9 +/- 5.3 cmH2O, and from 85.3 +/- 7.9 to 77.5 +/- 4.8 cmH2O, for PImax and PEmax, respectively) and increased during the PSV session (from 71.6 +/- 8.6 to 83.9 +/- 8.7 cmH2O, and from 80.4 +/- 7.8 to 88.0 +/- 7.4 cmH2O, for PImax and PEmax, respectively). The decrease in PEmax was significantly correlated with the severity of bronchial obstruction as evaluated based on baseline FEV1 (% predicted). Forced expiratory flows did not change after either CPT session. The amount of sputum expectorated was similar for the two CPT sessions (5.3 +/- 5.3 g vs 4.6 +/- 4.8 g after the control and PSV session, respectively; NS). Fifteen patients felt less tired after the PSV session. Ten patients reported that expectoration was easier with PSV, whereas 4 did not note any difference; 2 patients did not expectorate. Nine patients expressed a marked and 5 a small preference for PSV, and 2 patients had no preference. The physiotherapists found it easier to perform CPT with PSV in 14 patients and did not perceive any difference in 2 patients. DISCUSSION: Our study in CF children shows that respiratory muscle performance, as evaluated based on various parameters, decreased after CPT and that significant falls in oxygen saturation occurred after the FET maneuvers despite the quiet breathing periods between each FET cycle. These unwanted effects of CPT were