***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: A double-blind study was design ed to establish the residual effects of zopiclone on performance in healthy volunteers . 10 healthy male volunteers aged 22 - 45 years ( mean age 27.4 years ) were included in this study . 6 of the volunteers were cigar/cigarette smokers and were asked to smoke as little as possible on the study days . The subjects were r and omly allocated to a balanced design in which each subject received single oral doses of placebo , 2.5- , 5- , 7.5- and 10-mg tablets of zopiclone under double-blind conditions . A battery of tests were performed 10 and 13 h after overnight ingestion of the drug . The tests comprised : EEG , auditory reaction time , tapping rate , digit symbol substitution test , symbol copying test , mood rating scales , side effects rating scales , and subjective assessment s of sleep and performance .  Zopiclone is shown to have useful hypnotic properties but residual effects are detectable using EEG and psychological tests both 10 and 13 h after ingestion . The 10-mg dose significantly impairs performance the next day ; the 5-mg dose is almost devoid of residual psychomotor effects but is only marginally effective in hastening onset of sleep and does not improve sleep quality . The 7.5-mg dose has definite effects on sleep and limited residual effects the next day . No significant side effects were reported . In this study , using single doses in healthy subjects , the best balance between wanted hypnotic effects and unwanted residual effects the next day was provided by the 7.5-mg dose of zopiclone . It is recommended that further studies with repeated doses in healthy volunteer subjects and in insomniac patients use the 7.5-mg dose as the reference point STUDY OBJECTIVES To evaluate the effects of napping , caffeine , and napping plus caffeine on performance and alertness in both laboratory and field setting s. DESIGN ( 1 ) Laboratory Study : parallel-groups design with r and om assignment to 1 of 4 experimental conditions . ( 2 ) Field Study : crossover design . SETTING Sleep laboratory and field setting s. PARTICIPANTS ( 1 ) Laboratory Study : 68 healthy individuals ; ( 2 ) Field Study : 53 shiftworkers who worked nights or rotating shifts . INTERVENTIONS ( 1 ) Laboratory Study : an evening nap opportunity before the first 2 of 4 consecutive simulated night shifts plus placebo taken all 4 nights , caffeine taken nightly , the combination of the nap and caffeine conditions , or placebo . ( 2 ) Field Study : an evening nap on the first 2 of 4 consecutive night shifts plus caffeine taken nightly versus placebo taken nightly without naps . MEASUREMENTS AND RESULTS ( 1 ) Laboratory Study : Napping , caffeine , and their combination all improved alertness and performance as measured by Maintenance of Wakefulness Test and Psychomotor Vigilance Task , but the combination of napping and caffeine was best in improving alertness . ( 2 ) Field Study : Napping plus caffeine improved performance as measured by Psychomotor Vigilance Test and decreased subjective sleepiness in individuals working the night shift . CONCLUSIONS Napping plus caffeine helps improve performance and alertness of night-shift workers This study examined the impact of eating during simulated night shift on performance and subjective complaints . Subjects were r and omized to eating at night ( n=5 ; 23.2 ± 5.5 y ) or not eating at night ( n=5 ; 26.2 ± 6.4 y ) . All participants were given one sleep opportunity of 8 h ( 22:00 h-06:00 h ) before transitioning to the night shift protocol . During the four days of simulated night shift participants were awake from 16:00 h-10:00 h with a daytime sleep of 6 h ( 10:00 h-16:00 h ) . In the simulated night shift protocol , meals were provided at ≈0700 h , 1900 h and 0130 h ( eating at night ) ; or ≈0700 h , 0930 h , 1410 h and 1900 h ( not eating at night ) . Subjects completed sleepiness , hunger and gastric complaint scales , a Digit Symbol Substitution Task and a 10-min Psychomotor Vigilance Task . Increased sleepiness and performance impairment was evident in both conditions at 0400 h ( p<0.05 ) . Performance impairment at 0400 h was exacerbated when eating at night . Not eating at night was associated with elevated hunger and a small but significant elevation in stomach upset across the night ( p<0.026 ) . Eating at night was associated with elevated bloating on night one , which decreased across the protocol . Restricting food intake may limit performance impairments at night . Dietary recommendations to improve night-shift performance must also consider worker comfort Various combinations of interventions were used to phase-delay circadian rhythms to correct their misalignment with night work and day sleep . Young participants ( median age = 22 , n= 67 ) participated in 5 consecutive simulated night shifts ( 2300 to 0700 ) and then slept at home ( 0830 to 1530 ) in darkened bedrooms . Participants wore sunglasses with normal or dark lenses ( transmission 15 % or 2 % ) when outside during the day . Participants took placebo or melatonin ( 1.8 mg sustained release ) before daytime sleep . During the night shifts , participants were exposed to a moving ( delaying ) pattern of intermittent bright light ( ~5000 lux , 20 min on , 40 min off , 4 - 5 light pulses/night ) or remained in dimlight ( ~150 lux ) . There were 6 intervention groups ranging fromthe least complex ( normal sunglasses ) to the most complex ( dark sunglasses + bright light + melatonin ) . The  dim light melatonin onset ( DLMO ) was assessed before and after the night shifts ( baseline and final ) , and 7 h was added to estimate the temperature minimum ( Tmin ) . Participants were categorized by their amount of reentrainment based on their final Tmin : not re-entrained ( Tmin before the daytime dark/sleep period ) , partially re-entrained ( Tmin during the first half of dark/sleep ) , or completely re-entrained ( Tmin during the second half of dark/ sleep ) . The sample was split into earlier participants ( baseline Tmin = 0700 , sunlight during the commute home fell after the Tmin ) and later participants ( baseline Tmin > 0700 ) . The later participants were completely re-entrained regardless of intervention group , whereas the degree of re-entrainment for the earlier participants depended on the interventions . With bright light during the night shift , almost all of the earlier participants achieved complete re-entrainment , and the phase delay shift was so large that darker sunglasses and melatonin could not increase its magnitude . With only room light during the night shift , darker sunglasses helped earlier participants phase-delay more than normal sunglasses , but melatonin did not increase the phase delay . The authors recommendthecombination of intermittent bright light during the night shift , sunglasses ( as dark as possible ) during the commute home , and a regular , early daytime dark/sleep period if the goal is complete circadian adaptation to night-shift work UNLABELLED We investigated the effect of adapted management of sleep on the duration and quality of sleep in shift workers working the night shift . Twenty-nine shift workers suffering from insomnia were included and treated with zopiclone ( 7.5mg/day ) or placebo according to a r and om double-blind protocol . Patients completed a sleep diary and a wrist actigraph was used to evaluate episodes of rest/activity . A self-administered subjective sleep question naire was filled out just after awakening . Zopicone was found to increase the duration of sleep significantly ( p<0.05 ) over the baseline duration after the first and second night on duty . Subjective estimation of sleep was better in patients taking zopiclone who exhibited a smaller number of shorter awakening episodes . IN CONCLUSION zopiclone improves the quality and duration of sleep in shift workers suffering from insomnia Background Average bioequivalence has been criticized for not adequately addressing individual variations . Importance of subjects ' blinding in bioequivalence studies has not been well studied . We explored the extent of intra-subject pharmacokinetic variability and effect of drug-ingestion unawareness in subjects taking single caffeine product . Methods A single-dose r and omized cross-over design was used to compare pharmacokinetics of 200 mg caffeine , described as caffeine ( overt ) or as placebo ( covert ) . Maximum concentration ( Cmax ) , Cmax first time ( Tmax ) , area-under-the-concentration-time-curve , to last measured concentration ( AUCT ) , extrapolated to  infinity  ( AUCI ) , or to Tmax of overt caffeine ( AUCOverttmax ) , and Cmax/AUCI were calculated blindly using st and ard non-compartmental method . Percentages of individual covert/overt ratios that are outside the ±25 % range were determined . Covert-vs-overt effect on caffeine pharmacokinetics was evaluated by 90 % confidence interval ( CI ) and 80.00 - 125.00 % bioequivalence range . Results 32 healthy subjects ( 6 % females , mean ( SD ) age 33.3 ( 7.2 ) year ) participated in the study ( 28 analysed ) . Out of the 28 individual covert/overt ratios , 23 % were outside the ±25 % range for AUCT , 30 % for AUCI , 20 % for AUCOverttmax , 30 % for Cmax , and 43 % for Tmax . There was no significant covert-vs-overt difference in any of the pharmacokinetic parameters studied . Further , the 90 % CIs for AUCT , AUCI , Cmax , AUCOverttmax , and Cmax/AUCI were all within the 80.00 - 125.00 % bioequivalence range with mean absolute deviation of covert/overt ratios of 3.31 % , 6.29 % , 1.43 % , 1.87 % , and 5.19 % , respectively . Conclusions Large intra-subject variability in main caffeine pharmacokinetic parameters was noted when comparing an oral caffeine product to itself . Subjects ' blinding may not be important in average bioequivalence studies Caffeine promotes wakefulness during night shift work , although it also disturbs subsequent daytime sleep . Increased alertness by caffeine is associated with a higher core body temperature ( CBT ) . A lower CBT and a narrow distal-to-proximal skin temperature gradient ( DPG ) have been reported to be associated with improved sleep , yet whether caffeine influences the DPG is unknown . We tested the hypothesis that the use caffeine during nighttime total sleep deprivation would reduce the DPG , increase CBT and alertness , and disturb subsequent daytime recovery sleep . We also expected that a greater widening of the DPG prior to sleep would be associated with a greater degree of sleep disturbance . Thirty healthy adults ( 9 females ) aged 21.6 ± 3.5 years participated in a double-blind , 28-h modified constant routine protocol . At 23 h of wakefulness , participants in the treatment condition ( n = 10 ) were given 2.9 mg/kg caffeine , equivalent to ~200 mg ( or 2 espressos ) for a 70-kg adult , 5 h before a daytime recovery sleep episode . Throughout the protocol , core and skin body temperatures , DPG , sleep architecture , and subjective alertness and mood were measured . Prior to sleep , caffeine significantly widened the DPG and increased CBT , alertness , and clear-headedness ( p < 0.05 ) . Caffeine also disturbed daytime recovery sleep ( p < 0.05 ) . Increased CBT and a wider DPG prior to sleep were associated with a longer latency to sleep , and a wider DPG was associated with disturbed recovery sleep ( i.e. , increased wakefulness after sleep onset , increased stage 1 sleep , decreased sleep efficiency , and decreased slow wave sleep ) ( p < 0.05 ) . A widening of the DPG following nighttime caffeine may represent a component of the integrated physiological response by which caffeine  improves alertness and disturbs subsequent daytime recovery sleep . Furthermore , our findings highlight that sleep disturbances associated with caffeine consumed near the circadian trough of alertness are still present when daytime recovery sleep occurs 5 h or approximately 1 half-life later 
    Output:
    
Fifty seven per cent described an accident or near-miss travelling home from night shifts.5 Performance on night shift declines with