***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: Context Recent reports suggest that antipsychotics are associated with increased risk for death in patients with dementia . Contribution This large , population -based study from Canada assessed the risk for death after dispensation of antipsychotics in older adults with dementia . New use of antipsychotics compared with nonuse was associated with increased risk for death at 30 days . Conventional agents were associated with higher risks than were atypical agents . Caution Sensitivity analyses showed that unmeasured confounders might diminish or erase observed associations . Implication Both conventional and atypical antipsychotics may be associated with an increased risk for death in elderly persons with dementia . The Editors Various challenging behavioral and psychological symptoms commonly develop in older adults with dementia and predispose them and their caregivers to poor outcomes ( 1 ) . Nonpharmacologic strategies are recommended as first-line management for these symptoms ( 2 ) , but they may be difficult to implement in clinical practice ( 3 ) . For many reasons , antipsychotic medications are routinely prescribed in this setting ( 4 , 5 ) . Conventional antipsychotics , such as haloperidol , have been available since the 1950s . Meta-analyses of clinical trials evaluating conventional antipsychotics to treat agitation in dementia show that these agents have modest efficacy and important adverse effects compared with placebo ( 6 , 7 ) . In the past decade , use of newer atypical antipsychotics has been rapidly increasing in clinical practice because these agents were thought to produce fewer adverse effects than conventional agents ( 2 ) . A Canadian study found that the prevalence of antipsychotic use in older adults increased from 2.2 % in 1993 to 3.0 % at the end of 2002 . In that study , atypical antipsychotics , which were unavailable in 1993 , accounted for 82.5 % of all antipsychotics dispensed in 2002 ( 8) . Short-term r and omized , controlled trials ( RCTs ) have studied the role of atypical antipsychotics in the management of behavioral and psychological symptoms of dementia ( 2 , 9 ) . An RCT involving 421 out patients with Alzheimer disease and psychosis , aggression , or agitation concluded that the adverse effects of these newer drugs offset their advantages ( 10 ) . As a result , improvements in behavioral symptoms with antipsychotic drug treatment do not necessarily lead to improvements in overall quality of life for patients or their caregivers ( 11 ) . In April 2005 , the U.S. Food and Drug Administration ( FDA ) issued a public health advisory that the use of atypical antipsychotics to treat elderly patients with dementia was associated with an increased risk for death compared with placebo ( 12 ) . In June 2005 , Health Canada issued a similar warning and additional data ( 13 ) . These warnings stem from review s of RCTs that involve the atypical agents risperidone , olanzapine , quetiapine , and aripiprazole . The mortality rate was approximately 1.6 to 1.7 times higher than with placebo and was greater with antipsychotics than with placebo in 15 of the 17 trials review ed by the U.S. FDA ( 12 ) . The warnings extend to all currently available atypical antipsychotics . Other publications have provided support for these warnings and have raised further safety concerns about older conventional antipsychotics ( 1416 ) . Important questions remain unanswered . Although RCTs provide the best evidence of treatment efficacy and harm , the individual RCTs in this case had low event rates . Reliable estimates of the mortality risk were generated only when data were combined by meta- analysis ( 14 ) . Furthermore , these RCTs were generally short in duration and could not provide information about the long-term effect of antipsychotics on mortality ( 14 , 17 ) . Finally , these trials provide estimates of harm primarily for atypical antipsychotics . Relatively few data are available on harms associated with older conventional antipsychotics . Studies suggest that important differences may exist in the safety profiles of conventional and atypical agents ( 15 , 16 , 18 , 19 ) . Using population -based data , we sought to determine the risk for all-cause mortality in older adults with dementia who received atypical antipsychotics , conventional antipsychotics , or no antipsychotic .  Because important baseline differences exist among these groups , we used propensity score matching to improve their comparability . We also evaluated the effect of duration of treatment with antipsychotics on the risk for death . Methods Data Sources Ontario is Canada 's most populous province . During our study , Ontario had a population of approximately 12 million people , of whom 1.4 million were 65 years of age or older . A universally funded health program covers nearly all physician services , medications , and hospital services for patients 65 years of age or older in Ontario . Information from 4 administrative health care data bases was linked to develop the study cohort : pharmacy records from the Ontario Drug Benefit program , hospitalization records from the Canadian Institute for Health Information Discharge Abstract Data base , physician billing information for inpatient and outpatient services from the Ontario Health Insurance Plan , and basic demographic information and vital statistics from the Registered Persons Data base . We used encrypted unique identifiers that are common among data bases to link anonymous information on demographic characteristics and health services utilization for patients in our study . Little basic information on patients is missing in these data bases . For example , the coding accuracy of drug cl aims in the Ontario Drug Benefit program data base is excellent , with an error rate of only 0.7 % ( 20 ) . The study was approved by the ethics review board of Sunnybrook and Women 's College Health Sciences Centre , Toronto , Ontario , Canada . Dementia Cohort We identified a cohort of all Ontario residents 66 years of age or older with a diagnosis of dementia ( in the Ontario Health Insurance Plan or Discharge Abstract Data base ) between 1 April 1997 and 31 March 2002 . To focus on antipsychotic drug treatment for behavioral and psychological symptoms of dementia , we excluded patients who had evidence of other psychotic disorders ( such as schizophrenia ) or were receiving palliative care services . To reduce the potential for selection bias , we studied only new users of antipsychotics and excluded those who had received antipsychotics in the year before cohort entry ( 21 ) . Exposure to Antipsychotics We identified new use of antipsychotics if any agent available through the Ontario Drug Benefit program was dispensed after cohort entry . Cohort entry ( that is , the index date ) was defined as the date of the first dispensed antipsychotic drug . Available atypical drugs included olanzapine , quetiapine , and risperidone , and available conventional drugs included chlorpromazine , flupenthixol , fluphenazine , haloperidol , loxapine , pericyazine , perphenazine , pimozide , thioridazine , and trifluoperazine . Clozapine was rarely used in Ontario during the study period , and we therefore excluded patients who were receiving this medication . Other atypical antipsychotics ( such as aripiprazole and ziprasidone ) are not licensed for use in Canada . We decided that exposure to an antipsychotic was discontinued ( and we censored follow-up ) if the patient did not refill his or her antipsychotic prescription within an interval composed of the days of drug supply plus a grace period of 20 % . For example , we censored follow-up for a patient who did not refill his or her 60-day antipsychotic prescription within 72 days . We also censored follow-up for patients who switched from atypical to conventional antipsychotics ( or vice versa ) . However , we continued follow-up for patients who switched from 1 atypical antipsychotic to another , because data suggest no statistically significant difference in the risk for death associated with individual drugs in this class ( 13 , 14 , 16 ) . We applied the same rules to conventional antipsychotics .  All-Cause Mortality The primary outcome was all-cause mortality , as recorded in the Registered Persons Data base ( for patients who were not hospitalized at the time of death ) or the Discharge Abstract Data base ( for patients who died while hospitalized ) . To assess the influence of the duration of antipsychotic exposure on the outcome , we evaluated the risk for death at 30 , 60 , 120 , and 180 days after the initial dispensing of antipsychotic medication . Cohort Matching We stratified the dementia cohort to support separate analyses among persons living in the community and those residing in long-term care at cohort entry . Studies have demonstrated that rates of antipsychotic prescribing are substantial among older adults newly admitted to long-term care facilities ( 4 ) . Furthermore , long-term care residents typically carry a greater burden of comorbid disease and are more vulnerable to adverse drug events than are their counterparts in the community ( 22 , 23 ) . Our first objective was to determine the risk for death among older adults with dementia who received atypical antipsychotics compared with those who were not exposed to any antipsychotic .  Because antipsychotic use was not r and omly assigned in the study cohorts , we addressed potential confounding and selection biases by developing a propensity score for antipsychotic use . We then applied this score to match users of atypical antipsychotics with nonusers in the dementia cohort . The rationale and methods underlying the use of a propensity score for a proposed causal exposure variable are described elsewhere ( 24 ) . Recent studies provide guidance on the selection of variables to include in the propensity score ( 25 , 26 ) . We developed a logistic regression model by using 42 covariates describing patient characteristics . Tables 1 and 2 list many of the characteristics included in the propensity score . After a structured and iterative assessment of the balance of measured covariates BACKGROUND Delirium is an organic psychiatric syndrome characterized by fluctuating consciousness and impaired cognitive functioning . High-potency typical neuroleptics have traditionally been used as first-line drugs in the treatment of delirium . However , these drugs are frequently associated with undesirable adverse events including extrapyramidal symptoms ( EPS ) . The purpose of the present open-label , flexible-dose study was to provide preliminary data on the usefulness and safety of quetiapine for patients with delirium . METHOD Twelve patients with DSM-IV delirium were treated with flexible doses of open-label quetiapine ( mean + /- SD dosage = 44.9 + /- 31.0 mg/day ) . To evaluate the usefulness and safety of quetiapine , scores from the Delirium Rating Scale , Japanese version , were assessed every day ( for 1 outpatient , at least twice per week ) , and scores from the Mini-Mental State Examination , Japanese version , and the Drug-Induced Extrapyramidal Symptom Scale were assessed at baseline and after remission of delirium . Data were gathered from April to October 2001 . RESULTS All patients achieved remission of delirium several days after starting quetiapine ( mean + /- SD duration until remission = 4.8 + /- 3.5 days ) . Quetiapine treatment was well tolerated , and no clinical ly relevant change in EPS was detected . CONCLUSION Quetiapine may be a useful alternative to conventional neuroleptics in the treatment of delirium due to its rapid onset and relative lack of adverse events . Further double-blind , placebo-controlled studies are warranted The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . Perospirone is a recently developed atypical antipsychotic with potent serotonin 5-HT2 and dopamine D2 antagonist activity . Other atypical antipsychotics including risperidone , quetiapine and olanzapine have been widely used for treatment , not only for schizophrenia symptoms but also for delirium , because of their low potential to induce extrapyramidal disturbances . In the present study the effectiveness and safety of perospirone in patients with delirium are described . Thirty-eight patients with DSM-IV delirium were given open-label  perospirone . To evaluate the usefulness of perospirone , scores from 13 severity items of the Delirium Rating Scale-Revised-98 were assessed . Data were gathered from October 2003 to September 2004 . Perospirone was effective in 86.8 % ( 33/38 ) of patients , and the effect appeared within several days ( 5.1 + /- 4.9 days ) . The initial dose was 6.5 + /- 3.7 mg/day and maximum dose of perospirone was 10.0 + /- 5.3 mg/day . There were no serious adverse effects . However , increased fatigue ( 15.2 % ) , sleepiness ( 6.1 % ) , akathisia ( 3.0 % ) and a decline in blood pressure ( 3.0 % ) were observed . It is proposed that perospirone may be another safe and effective atypical antipsychotic drug for the treatment of delirium symptoms in hospitalized patients . This is a preliminary open trial , and further r and omized double-blind placebo-controlled tests are needed BACKGROUND Delirium is a commonly occurring complex neuropsychiatric disorder . Evidence for its treatment based on r and omized controlled trials ( RCTs ) is poor . AIMS To determine the efficacy and acceptability of quetiapine in the treatment of delirium . METHOD A double-blind , RCT was conducted . A total of 42 patients were r and omized to quetiapine or a placebo group . 
    Output:
    
CONCLUSION Because of severe method ological limitations , the studies in this review do not support the use of antipsychotics in the treatment of delirium in older hospitalized adults .