***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 We hypothesized that delirium symptoms may respond differently to antipsychotic therapy . The purpose of this paper was to retrospectively compare duration and time to first resolution of individual delirium symptoms from the data base of a r and omized , double-blind , placebo-controlled study comparing quetiapine ( Q ) or placebo ( P ) , both with haloperidol rescue , for critically ill patients with delirium . Methods Data for 10 delirium symptoms from the eight-domain , intensive care delirium screening checklist ( ICDSC ) previously collected every 12 hours were extracted for 29 study patients . Data between the Q and P groups were compared using a cut-off P- value of ≤0.10 for this exploratory study . Results Baseline ICDSC scores ( 5 ( 4 to 7 ) ( Q ) vs 5 ( 4 to 6 ) ) ( median , interquartile range ( IQR ) ) and % of patients with each ICDSC symptom were similar in the two groups ( all P > 0.10 ) . Among patients with the delirium symptom at baseline , use of Q may lead to a shorter time ( days ) to first resolution of symptom fluctuation ( 4 ( Q ) vs. 14 , P = 0.004 ) , inattention ( 3 vs. 8 , P = .10 ) and disorientation ( 2 vs. 10 , P = 0.10 ) but a longer time to first resolution of agitation ( 3 vs. 1 , P = 0.04 ) and hyperactivity ( 5 vs. 1 , P = 0.07 ) . Among all patients , Q-treated patients tended to spend a smaller percent of time with inattention ( 47 ( 0 to 67 ) vs. 78 ( 43 to 100 ) , P = 0.025 ) , hallucinations ( 0 ( 0 to 17 ) vs. 28 ( 0 to 43 ) , P = 0.10 ) and symptom fluctuation ( 47 ( 19 to 67 ) vs. 89 ( 33 to 00 ) , P = 0.04 ] and there was a trend for Q-treated patients to spend a greater percent of time at an appropriate level of consciousness ( 26 % ( 13 to 63 % ) vs. 14 % ( 0 to 33 % ) , P = 0.17 ] . Conclusions Our exploratory analysis suggests that quetiapine may resolve several intensive care unit ( ICU ) delirium symptoms faster than the placebo . Individual symptom resolution appears to differ in association with the pharmacologic intervention ( that is , P vs Q , both with as needed haloperidol ) . Future studies evaluating antipsychotics in ICU patients with delirium should measure duration and resolution of individual delirium symptoms and their relation to long-term outcomes Objective : To examine the impact of delirium during intensive care unit stay on long-term health-related quality of life and cognitive function in intensive care unit survivors . Design : Prospect i ve 18-month follow-up study . Setting : Four intensive care units of a university hospital . Patients : A median of 18 months after intensive care discharge , question naires were sent to 1,292 intensive care survivors with ( n = 272 ) and without ( n = 1020 ) delirium during their intensive care stay . Measurements and Main Results : The  Short Form-36v1 , checklist individual strength-fatigue , and cognitive failure question naire were used . Covariance analysis was performed to adjust for relevant covariates . Of the 915 responders , 171 patients were delirious during their intensive care stay ( median age 65 [ interquartile range 58–85 ] , Acute Physiology and Chronic Health Evaluation II score 17 [ interquartile range 14–20 ] ) , and 745 patients were not ( median age 65 [ interquartile range 57–72 ] , Acute Physiology and Chronic Health Evaluation II score 13 [ interquartile range 10–16 ] ) . After adjusting for covariates , no differences were found between delirium and nondelirium survivors on the Short Form-36 and checklist individual strength-fatigue . However , survivors who had suffered from delirium reported that they made significantly more social blunders , and their total cognitive failure question naire score was significantly higher , compared to survivors who had not been delirious . Survivors of a hypoactive delirium subtype performed significantly better on the domain mental health than mixed and hyperactive delirium patients . Duration of delirium was significantly correlated to problems with memory and names . Conclusions : Intensive care survivors with delirium during their intensive care unit stay had a similar adjusted health-related quality of life evaluation , but significantly more cognitive problems than those who did not suffer from delirium , even after adjusting for relevant covariates . In addition , the duration of delirium was related to long-term cognitive problems Introduction Delirium is a common , serious and potentially preventable condition with devastating impact on the quality of life prompting a proliferation of interventional trials . Core outcome sets aim to st and ardise outcome reporting by identifying outcomes perceived fundamental for measurement in trials of a specific interest area . Our aim is to develop international consensus on two core outcome sets for trials of interventions to prevent and /or treat delirium , irrespective of study population . We aim to identify additional core outcomes specific to the critically ill , acutely hospitalised patients , palliative care and older adults . Methods and analysis We will conduct a systematic review of published and ongoing delirium trials ( 1980 onwards ) and  one-on-one interviews of patients who have experienced delirium and family members . These data will inform Delphi round 1 of a two-stage consensus process . In round 2 , we will provide participants their own response , summarised group responses and those of patient/family participants for rescoring . We will r and omise participants to receive feedback as proportion scoring the outcome as critical or as group mean responses . We will hold a consensus meeting using nominal group technique to finalise outcomes for inclusion . We will repeat the Delphi process and consensus meeting to select measures for each core outcome . We will recruit 240 Delphi participants giving us 80 % power to detect a 1.0–1.5 point ( 9-point scale ) difference by feedback method between rounds . We will analyse differences for subsequent scores , magnitude of opinion change , items retained and level of agreement . Ethics and dissemination We are obtaining research ethics approvals according to local governance . Participation will be voluntary and data deidentified . Support from three international delirium organisations will be instrumental in dissemination and core outcome set uptake . We will disseminate through peer- review ed open access publications and present at conferences selected to reach a wide range of knowledge users BACKGROUND Delirium is common in mechanically ventilated patients and is associated with cognitive impairment lasting at least 1 year after hospital discharge . Pre clinical and observational studies suggest that the use of statins might reduce delirium in intensive care . We assessed whether the pleiotropic effects of statins can reduce delirium in intensive care and decrease subsequent cognitive impairment in a r and omised controlled trial . METHODS We did this ancillary study within the SAILS trial , a r and omised controlled trial assessing mortality and ventilator-free days for rosuvastatin versus placebo for patients with sepsis-associated acute respiratory distress syndrome . This study was done at 35 hospitals in the USA . Patients were r and omly assigned in permuted blocks of eight and stratified by hospital to receive either rosuvastatin ( 40 mg loading dose and then 20 mg daily until the earliest of 3 days after discharge from intensive care , study day 28 , or death ) or placebo . Patients and investigators were masked to treatment assignment . Delirium was assessed with the vali date d Confusion Assessment Method for intensive care . Cognitive function was assessed with tests for executive function , language , verbal reasoning and concept formation , and working , immediate , and delayed memory . We defined cognitive impairment as having one of these domains at least two SDs below population norms or at least two domains at least 1·5 SDs below norms . The primary endpoint was daily delirium status in intensive care up to 28 days in the intention-to-treat population and secondary endpoints were cognitive function at 6 months and 12 months . This trial is registered with Clinical Trials.gov ( NCT00979121 and NCT00719446 ) . FINDINGS 272 patients were assessed for delirium daily in intensive care . The mean proportion of days with delirium was 34 % ( SD 30 % ) in the rosuvastatin group versus 31 % ( 29 % ) in the placebo group ; hazard ratio 1·14 , 95 % CI 0·92 - 1·41 , p=0·22 . At 6 months , 19 ( 36 % ) of 53 patients in the rosuvastatin group versus 29 ( 38 % ) of 77 in the placebo group had cognitive impairment , with no significant difference between groups ( treatment effect 0·93 , 95 % CI 0·39 - 2·22 ; p=0·87 ) . At 12 months , 20 ( 30 % ) of 67 patients versus 23 ( 28 % ) of 81 patients had cognitive impairment , with no significant difference between groups ( treatment effect 1·1 , 95 % CI 0·5 - 2·6 ; p=0·82 ) . INTERPRETATION Most patients had delirium , with around a third of survivors having cognitive impairment over 1 year of follow-up . Despite encouraging pre clinical and observational studies , this trial shows no benefit of rosuvastatin in reducing delirium in intensive care or cognitive impairment during 12 months of follow-up although the study was not powered for superiority . Thus , there is continued need to evaluate interventions aim ed at attenuating intensive care and post-intensive-care cognitive impairments commonly observed in this population . FUNDING National Heart , Lung and Blood Institute ; Johns Hopkins Institute for Clinical and Translational Research ; the SAILS trial was also supported by AstraZeneca BACKGROUND  Delirium in critically ill patients is associated with poor clinical outcomes . Neuroinflammation might be an important mechanism in the pathogenesis of delirium , and since simvastatin has anti-inflammatory properties it might reduce delirium . We aim ed to establish whether early treatment with simvastatin would decrease the time that survivors of critical illness spent in delirium or coma . METHODS We undertook this r and omised , double-blind , placebo-controlled trial in a general adult intensive care unit ( ICU ) in Watford General Hospital ( Watford , UK ) . We enrolled critically ill patients ( ≥18 years ) needing mechanical ventilation within 72 h of admission . We r and omly assigned patients ( 1:1 ratio ) to receive either simvastatin 80 mg or placebo daily for up to a maximum of 28 days , irrespective of coma or delirium status . We assessed delirium using the Confusion Assessment Method for the ICU ( CAM-ICU ) . The primary outcome was number of days alive and was assessed as delirium-free and coma-free in the first 14 days after being r and omly allocated to receive treatment or placebo . ICU clinical and research staff and patients were masked to treatment . We did intention-to-treat analyses with no extrapolation . This trial is registered with the International St and ard R and omised Controlled Trial Registry , number IS RCT N89079989 . FINDINGS Between Feb 1 , 2013 , and July 29 , 2016 , 142 patients were r and omly assigned to receive simvastatin ( n=71 ) or placebo ( n=71 ) , and were included in the final analysis .  The mean number of days alive without delirium and without coma at day 14 did not differ significantly between the two groups ( 5·7 days [ SD 5·1 ] with simvastatin and 6·1 days [ 5·2 ] with placebo ; mean difference 0·4 days , 95 % CI -1·3 to 2·1 ; p=0·66 ) . The most common adverse event was an elevated creatine kinase concentration to more than ten times the upper limit of normal ( eight [ 11 % ] in the simvastatin group vs three [ 4 % ] in the placebo group p=0·208 ) . No patient had a serious adverse event related to the study drug . INTERPRETATION These results do not support the hypothesis that simvastatin modifies duration of delirium and coma in critically ill patients . FUNDING National Institute for Health Research Objective : To compare the efficacy and safety of scheduled quetiapine to placebo for the treatment of delirium in critically ill patients requiring as-needed haloperidol .  Design : Prospect i ve , r and omized , double-blind , placebo-controlled study . Setting : Three academic medical centers . Patients : Thirty-six adult intensive care unit patients with delirium ( Intensive Care Delirium Screening Checklist score ≥4 ) , tolerating enteral nutrition , and without a complicating neurologic condition . Interventions : Patients were r and omized to receive quetiapine 50 mg every 12 hrs or placebo . Quetiapine was increased every 24 hrs ( 50 to 100 to 150 to 200 mg every 12 hrs ) if more than one dose of haloperidol was given in the previous 24 hrs . Study drug was continued until the intensive care unit team discontinued it because of delirium resolution , therapy ≥10 days , or intensive care unit discharge . Measurements and Main Results : Baseline characteristics were similar 
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We found evidence that the alpha2 agonist dexmedetomidine may shorten delirium duration , although this small effect ( compared with placebo ) was seen in pairwise analyses based on a single study and was not seen in the NMA results .
Alpha2 agonists also ranked best for duration of mechanical ventilation and length of ICU stay , whereas the CHE inhibitor rivastigmine was associated with longer ICU stay .
We found no evidence of a difference between placebo and any drug in terms of delirium-free and coma-free days , days with coma , physical restraint use , length of stay , long-term cognitive outcomes , or mortality .