***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: Introduction Many intensive care patients experience sleep disruption potentially related tonoise , light and treatment interventions . The purpose of this study was tocharacterise , in terms of quantity and quality , the sleep of intensive care patients , taking into account the impact of environmental factors . Methods This observational study was conducted in the adult ICU of a tertiary referralhospital in Australia , enrolling 57 patients .  Polysomnography ( PSG ) was performedover a 24-hour period to assess the quantity ( total sleep time : hh : mm ) and quality ( percentage per stage , duration of sleep episode ) of patients ' sleep while in ICU.Rechtschaffen and Kales criteria were used to categorise sleep . Interrater checkswere performed . Sound pressure and illuminance levels and care events weresimultaneously recorded . Patients reported on their sleep quality in ICU using theRichards Campbell Sleep Question naire and the Sleep in Intensive Care Question naire . Data were summarised using frequencies and proportions or measures of central tendency and dispersion as appropriate and Cohen 's Kappa statistic wasused for interrater reliability of the sleep data analysis . Results Patients ' median total sleep time was 05:00 ( IQR : 02:52 to 07:14 ) . The majority ofsleep was stage 1 and 2 ( medians : 19 and 73 % ) with scant slow wave and REM sleep . The median duration of sleep without waking was 00:03 . Sound levels were high(mean Leq 53.95 dB(A ) during the day and 50.20 dB(A ) at night ) and illuminancelevels were appropriate at night ( median < 2 lux ) but low during the day(median : 74.20 lux ) . There was a median 1.7 care events/h . Patients ' meanself-reported sleep quality was poor . Interrater reliability of sleep staging washighest for slow wave sleep and lowest for stage 1 sleep . Conclusions The quantity and quality of sleep in intensive care patients are poor and may berelated to noise , critical illness itself and treatment events that disturb sleep . The study highlights the challenge of quantifying sleep in the critical care setting and the need for alternative methods of measuring sleep . The results suggest that a sound reduction program is required and other interventions toimprove clinical practice s to promote sleep in intensive care patients .Trial registration Australian New Zeal and clinical trial registry(http://www.anzctr.org.au/ ) : ACTRN12610000688088 IMPORTANCE No highly effective interventions to prevent delirium have been identified . OBJECTIVE To examine whether ramelteon , a melatonin agonist , is effective for the prevention of delirium . DESIGN , SETTING , AND PARTICIPANTS A multicenter , rater-blinded , r and omized placebo-controlled trial was performed in intensive care units and regular acute wards of 4 university hospitals and 1 general hospital . Eligible patients were 65 to 89 years old , newly admitted due to serious medical problems , and able to take medicine orally . Patients were excluded from the study if they had an expected stay or life expectancy of less than 48 hours . INTERVENTIONS Sixty-seven patients were r and omly assigned using the sealed envelope method to receive ramelteon ( 8 mg/d ; 33 patients ) or placebo ( 34 patients ) every night for 7 days . MAIN OUTCOMES AND MEASURES Incidence of delirium , as defined by the Diagnostic and Statistical Manual of Mental Disorders ( Fourth Edition ) . RESULTS Ramelteon was associated with a lower risk of delirium ( 3 % vs 32 % ; P = .003 ) , with a relative risk of 0.09 ( 95 % CI , 0.01 - 0.69 ) . Even after risk factors were controlled for , ramelteon was still associated with a lower incidence of delirium ( P = .01 ; odds ratio , 0.07 [ 95 % CI , 0.008 - 0.54 ] ) . The Kaplan-Meier estimates of time to development of delirium were 6.94 ( 95 % CI , 6.82 - 7.06 ) days for ramelteon and 5.74 ( 5.05 - 6.42 ) days for placebo . Comparison by log-rank test showed that the frequency of delirium was significantly lower in patients taking ramelteon  than in those taking placebo ( χ(2 ) = 9.83 ; P = .002 ) . CONCLUSIONS AND RELEVANCE Ramelteon administered nightly to elderly patients admitted for acute care may provide protection against delirium . This finding supports a possible pathogenic role of melatonin neurotransmission in delirium . TRIAL REGISTRATION University Hospital Medical Information Network Clinical Trials Registry Identifier : UMIN000005591 Context : Little is known about the relationship between sedative drugs used preoperatively and postoperative delirium . Melatonin is a drug used to se date patients preoperatively and is hypothesized by recent works to have a curative effect on postoperative delirium . Aims : The incidence of postoperative delirium will be tested if affected by three different sedative drugs including melatonin . Setting s and Design : Controlled r and omized doubleblind study . Patients and Methods : Three-hundred patients aged>65 years scheduled for hip arthroplasty under spinal anesthesia were r and omly distributed to one of the four groups . Group 1 ( control ) received nothing for sedation . Group 2 ( melatonin ) received 5 mg melatonin . Group 3 ( midazolam ) received 7.5 mg midazolam . Group 4 ( clonidine ) received 100 μg clonidine . These medications were given orally at sleep time at night of operation and another dose 90 min before operative time . Patients who developed postoperative delirium received 5 mg of melatonin 9 pm for three successive days in a trial to treat delirium . Statistical Analysis Used : Statistical analysis was done using the SPSS Software ( version 13 ) . Results : Total of 222 patients completed the study . Percentage of postoperative delirium in the control group was 32.65 % ( 16/49 patients ) . The melatonin group showed a statistically significant decrease in the percentage of postoperative delirium to 9.43 % ( 5/53 patients ) . Melatonin was successful in treating 58.06 % of patients suffered postoperative delirium ( 36/62 patients ) with no difference between different groups . Conclusions : Postoperative delirium is affected with the drug used for preoperative sedation . Melatonin was successful in decreasing postoperative delirium when used preoperatively and in treating more than half of patients developed postoperative delirium when used for three postoperative nights CONTEXT In the intensive care unit ( ICU ) , delirium is a common yet underdiagnosed form of organ dysfunction , and its contribution to patient outcomes is unclear . OBJECTIVE To determine if delirium is an independent predictor of clinical outcomes , including 6-month mortality and length of stay among ICU patients receiving mechanical ventilation . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study enrolling 275 consecutive mechanically ventilated patients admitted to adult medical and coronary ICUs of a US university-based medical center between February 2000 and May 2001 . Patients were followed up for development of delirium over 2158 ICU days using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale . MAIN OUTCOME MEASURES Primary outcomes included 6-month mortality , overall hospital length of stay , and length of stay in the post-ICU period . Secondary outcomes were ventilator-free days and cognitive impairment at hospital discharge . RESULTS Of 275 patients , 51 ( 18.5 % ) had persistent coma and died in the hospital . Among the remaining 224 patients , 183 ( 81.7 % ) developed delirium at some point during the ICU stay . Baseline demographics including age , comorbidity scores , dementia scores , activities of daily living , severity of illness , and admission diagnoses were similar between those with and without delirium ( P>.05 for all ) . Patients who developed delirium had higher 6-month mortality rates ( 34 % vs 15 % , P = .03 ) and spent 10 days longer in the hospital than those who never developed delirium ( P<.001 ) . After adjusting for covariates ( including age , severity of illness , comorbid conditions , coma , and use of sedatives or analgesic medications ) , delirium was independently associated with higher 6-month mortality ( adjusted hazard ratio [ HR ] , 3.2 ; 95 % confidence interval [ CI ] , 1.4 - 7.7 ; P = .008 ) , and longer hospital stay ( adjusted HR , 2.0 ; 95 % CI , 1.4 - 3.0 ; P<.001 ) . Delirium in the ICU was also independently associated with a longer post-ICU stay ( adjusted HR , 1.6 ; 95 % CI , 1.2 - 2.3 ; P = .009 ) , fewer median days alive and without mechanical ventilation ( 19 [ interquartile range , 4 - 23 ] vs 24 [ 19 - 26 ] ; adjusted P = .03 ) , and a higher incidence of cognitive impairment at hospital discharge ( adjusted HR , 9.1 ; 95 % CI , 2.3 - 35.3 ; P = .002 ) . CONCLUSION Delirium was an independent predictor of higher 6-month mortality and longer hospital stay even after adjusting for relevant covariates including coma , sedatives , and analgesics in patients receiving mechanical ventilation Background Sleep deprivation is common in critically ill patients in intensive care units ( ICU ) . It can result in delirium , difficulty weaning , repeated nosocomial infections , prolonged ICU length of stay and increased ICU mortality .  Melatonin , a physiological sleep regulator , is well known to benefit sleep quality in certain people , but evidence for the effectiveness in ICU sleep disturbance is limited . Methods / Design This study has a prospect i ve , r and omized , double-blind , controlled , parallel-group design . Eligible patients are r and omly assigned to one of the two treatment study groups , labelled the ‘ melatonin group ’ or the ‘ placebo group ’ . A dose of 3 mg of oral melatonin or placebo is administered at 9:00 pm on four consecutive days . Earplugs and eye masks are made available to every participant . We plan to enrol 198 patients . The primary outcome is the objective sleep quality measured by the 24-hour polysomnography . The secondary outcomes are the subjective sleep quality assessed by the Richards Campbell Sleep Question naire , the anxiety level evaluated by the Visual Analogue Scale-Anxiety , the number of delirium-free days in 8 and 28 days , the number of ventilation-free days in 28 days , the number of antibiotic-free days , ICU length of stay , the overall ICU mortality in 28 days and the incidence and severity of the side effects of melatonin  in ICU patients . Additionally , the body stress levels , oxidative stress levels and inflammation levels are obtained via measuring the plasma melatonin , cortisone , norepinephrine , malonaldehyde(MDA ) , superoxide dismutase(SOD ) , interleukin-6 ( IL-6 ) and interleukin-8 (IL-8)concentrations . Discussion The proposed study will be the first r and omized controlled study to use the polysomnography , which is the gold st and ard of assessing sleep quality , to evaluate the effect of melatonin on the sleep quality and circadian rhythms of ICU patients . The results may recommend a new treatment for ICU patients with sleep deprivation that is safe , effective and easily implementable in daily practice .Trial registration This study was registered with Clinical Trials ( NCT ; registration number : ChiCTR-TRC-14004319 ) on 4 March 2013 BACKGROUND Disturbance in the metabolism of tryptophan and tryptophan-derived compounds ( e.g. , melatonin ) may have a role in the pathogenesis of delirium . OBJECTIVE To evaluate the efficacy of low dose exogenous melatonin in decreasing delirium . DESIGN A r and omized , double-blinded , placebo-controlled study . SETTING An Internal Medicine service in a tertiary care centre in London , Ontario , Canada . PARTICIPANTS 145 individuals aged 65 years or over admitted through the emergency department to a medical unit in a tertiary care hospital . INTERVENTION Patients were r and omized to receive either 0.5 mg of melatonin or placebo every night for 14 days or until discharge . MEASUREMENTS The primary outcome was the occurrence of delirium as determined by Confusion Assessment Method ( CAM ) criteria . RESULTS Of a total of 145 individuals ( mean age ( st and ard deviation ) : 84.5 ( 6.1 ) years ) 72 were r and omly assigned to the melatonin group and 73 to the placebo group . Melatonin was associated with a lower risk of delirium ( 12.0 % vs. 31.0 % , p = 0.014 ) , with an odds ratio ( OR ) , adjusted for dementia and co-morbidities of 0.19 ( 95 % confidence intervals ( CI ) : 0.06 - 0.62 ) . Results were not different when patients with prevalent delirium were excluded . LIMITATION An intention to treat analysis was not possible due to loss to follow-up . CONCLUSION Exogenous low dose melaton 
    Output:
    
FINDINGS Six primary research articles that investigated different methods of chronotherapy were identified , and the results suggest that multi-component non-pharmacological interventions are the most effective for reducing the prevalence of delirium in critical care .
Multi-component non-pharmacological interventions , such as noise and light control , can reduce delirium in critical care , whereas other interventions , such as BLT , have mixed outcomes .
Melatonin , as a drug , may be a useful alternative to sedative-hypnotics .
RELEVANCE TO CLINICAL PRACTICE Chronotherapy can reduce the incidence of delirium within critical care , although further research is warranted .