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1.  Systematic detection and multidisciplinary care of delirium in older medical inpatients: a randomized trial 
Delirium is common and often goes undetected in older patients admitted to medical services. It is associated with poor outcomes. We conducted a randomized clinical trial to determine whether systematic detection and multidisciplinary care of delirium in older patients admitted to a general medical service could reduce time to improvement in cognitive status.
Consecutive patients aged 65 or more who were newly admitted to 5 general medical units between Mar. 15, 1996, and Jan. 31, 1999, were screened with the Confusion Assessment Method within 24 hours after admission to detect prevalent delirium and rescreened within a week to detect incident cases. Patients with delirium were randomly allocated to receive the intervention or usual care. Subjects in the intervention group were seen by a geriatric specialist consultant and followed in hospital for up to 8 weeks by an intervention nurse who liaised with the consultant, attending physicians, family and the primary care nurses. Subjects in the usual care group received standard hospital services but could consult geriatric specialists as needed. A research assistant, blinded as to treatment allocation, administered within 24 hours after enrolment the Mini-Mental Status Exam (MMSE), Delirium Index (measuring the severity of the delirium) and Barthel Index (measuring independence of personal care). Improvement was defined as an increase in the MMSE score of 2 or more points, with no decrease below baseline plus 2 points, or no decrease below a baseline MMSE score of 27. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly was completed to identify patients with possible dementia. Subjects were assessed 3 times during the first week and weekly thereafter for up to 8 weeks in hospital or until discharge. Data on clinical severity of illness, length of stay and living arrangements after discharge were also collected. The primary outcome measure was time to improvement in MMSE score.
Of the 1925 patients who met the inclusion criteria and were screened, 227 had prevalent or incident delirium and consented to participate (113 in intervention group and 114 in usual care group). There were no clinically significant differences between the intervention and usual care groups except for sex (female 58.4% v. 50.0%) and marital status (married 34.8% v. 41.2%). Overall, 48% of the patients in the intervention group and 45% of those in the usual care group met the predetermined criteria for improvement. The Cox proportional hazards ratio (HR) for a shorter time to improvement with the intervention versus usual care, adjusted for age, sex and marital status, was 1.10 (95% confidence interval [CI] 0.74–1.63). There were no significant differences within 8 weeks after enrolment between the 2 groups in time to and rate of improvement of the Delirium Index, the Barthel Index, length of stay, rate of discharge to the community, living arrangements after discharge or survival. Outcomes between the 2 groups did not differ statistically significantly for patients without dementia (HR 1.54, 95% CI 0.80–2.97), for those who had less comorbidity (HR 1.36, 95% CI 0.75–2.46) or for those with prevalent delirium (HR 1.15, 95% CI 0.48–2.79).
Systematic detection and multidisciplinary care of delirium does not appear to be more beneficial than usual care for older patients admitted to medical services.
PMCID: PMC126506  PMID: 12389836
2.  Risk factors for delirium in acutely admitted elderly patients: a prospective cohort study 
BMC Geriatrics  2005;5:6.
Delirium is a neuropsychiatric syndrome frequently observed in elderly hospitalised patients and can be found in any medical condition. Due to the severe consequences, early recognition of delirium is important in order to start treatment in time. Despite the high incidence rate, the occurrence of delirium is not always identified as such. Knowledge of potential risk factors is important. The aim of the current study is to determine factors associated with the occurrence of a prevalent delirium among elderly patients acutely admitted to an internal medicine ward.
All consecutive patients of 65 years and over acutely admitted to the Department of Internal Medicine of the Academic Medical Centre, Amsterdam, a university hospital, were asked to participate. The presence of delirium was determined within 48 hrs after admission by an experienced geriatrician.
In total, 126 patients were included, 29% had a prevalent delirium after acute admission. Compared to patients without delirium, patients with delirium were older, more often were cognitively and physically impaired, more often were admitted due to water and electrolyte disturbances, and were less often admitted due to malignancy or gastrointestinal bleeding. Independent risk factors for having a prevalent delirium after acute admission were premorbid cognitive impairment, functional impairment, an elevated urea nitrogen level, and the number of leucocytes.
In this study, the most important independent risk factors for a prevalent delirium after acute admission were cognitive and physical impairment, and a high serum urea nitrogen concentration. These observations might contribute to an earlier identification and treatment of delirium in acutely admitted elderly patients.
PMCID: PMC1097727  PMID: 15826320
3.  Documentation of delirium in the VA electronic health record 
BMC Research Notes  2014;7:208.
Delirium is a life-threatening, clinical syndrome common among the elderly and hospitalized patients. Delirium is under-recognized and misdiagnosed, complicating efforts to study the epidemiology and construct appropriate decision support to improve patient care. This study was primarily conducted to realize how providers documented confirmed cases of delirium in electronic health records as a preliminary step for using computerized methods to identify patients with delirium from electronic health records.
The Mental Health Consult (MHC) team reported cases of delirium to the study team during a 6-month study period (December 1, 2009 - May 31, 2010). A chart extraction tool was developed to abstract documentation of diagnosis, signs and symptoms and known risk factors of delirium. A nurse practitioner, and a clinical pharmacist independently reviewed clinical notes during each patients hospital stay to determine if delirium and or sign and symptoms of delirium were documented.
The MHC team reported 25 cases of delirium. When excluding MHC team notes, delirium was documented for 5 of the 25 patients (one reported case in a physician’s note, four in discharge summaries). Delirium was ICD-9 Coded for 7 of the 25 cases. Signs and symptoms associated with delirium were characterized in 8 physician notes, 11 discharge summaries, and 14 nursing notes, accounting for 16 of the 25 cases with identified delirium.
Documentation of delirium is highly inconsistent even with a confirmed diagnosis. Hence, efforts to use existing data to precisely estimate the prevalence of delirium or to conduct epidemiological studies based on medical records will be challenging.
PMCID: PMC3985575  PMID: 24708799
4.  “Delirium superimposed on dementia is associated with prolonged length of stay and poor outcomes in hospitalized older adults” 
Current literature does not identify the significance of underlying cognitive impairment and delirium on older adults during and 30 days following acute care hospitalization.
Describe the incidence, risk factors, and outcomes associated with incident delirium superimposed on dementia.
24-month prospective cohort study
community hospital
139 older adults (>65 years) with dementia
This prospective study followed patients daily during hospitalization and one month post-hospital. Main measures included dementia (Modified Blessed Dementia Rating Score, IQ CODE), daily mental status change, dementia stage/severity (Clinical Dementia Rating, Global Deterioration Scale), delirium (Confusion Assessment Method), and delirium severity (Delirium Rating Scale-Revised-98). All statistical analysis was performed using SAS 9.3 and significance with an alpha level of 0.05. Logistic regression, analysis of covariance or linear regression was performed controlling for age, gender and dementia stage.
The overall incidence of new delirium was 32% (44/140). Those with delirium had a 25% short term mortality rate, increased length of stay and poorer function at discharge. At one month follow-up, subjects with delirium had greater functional decline. Males were more likely to develop delirium and for every one unit increase in dementia severity (Global Deterioration Scale), subjects were 1.5 times more likely to develop delirium.
Delirium prolongs hospitalization for persons with dementia. Thus, interventions to increase early detection of delirium have the potential to decrease the severity and duration of delirium and to prevent unnecessary suffering and costs from the complications of delirium and unnecessary readmissions to the hospital.
PMCID: PMC3928030  PMID: 23955965
5.  Delirium in an adult acute hospital population: predictors, prevalence and detection 
BMJ Open  2013;3(1):e001772.
To date, delirium prevalence and incidence in acute hospitals has been estimated from pooled findings of studies performed in distinct patient populations.
To determine delirium prevalence across an acute care facility.
A point prevalence study.
A large tertiary care, teaching hospital.
311 general hospital adult inpatients were assessed over a single day. Of those, 280 had full data collected within the study's time frame (90%).
Initial screening for inattention was performed using the spatial span forwards and months backwards tests by junior medical staff, followed by two independent formal delirium assessments: first the Confusion Assessment Method (CAM) by trained geriatric medicine consultants and registrars, and, subsequently, the Delirium Rating Scale-Revised-98 (DRS-R98) by experienced psychiatrists. The diagnosis of delirium was ultimately made using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria.
Using DSM-IV criteria, 55 of 280 patients (19.6%) had delirium versus 17.6% using the CAM. Using the DRS-R98 total score for independent diagnosis, 20.7% had full delirium, and 8.6% had subsyndromal delirium. Prevalence was higher in older patients (4.7% if <50 years and 34.8% if >80 years) and particularly in those with prior dementia (OR=15.33, p<0.001), even when adjusted for potential confounders. Although 50.9% of delirious patients had pre-existing dementia, it was poorly documented in the medical notes. Delirium symptoms detected by medical notes, nurse interview and patient reports did not overlap much, with inattention noted by professional staff, and acute change and sleep-wake disturbance noted by patients.
Our point prevalence study confirms that delirium occurs in about 1/5 of general hospital inpatients and particularly in those with prior cognitive impairment. Recognition strategies may need to be tailored to the symptoms most noticed by the detector (patient, nurse or primary physician) if formal assessments are not available.
PMCID: PMC3549230  PMID: 23299110
Geriatric Medicine; Mental Health; Epidemiology; Internal Medicine; Medical Education & Training
6.  A Quality Assurance Study to Assess the One-Day Prevalence of Delirium in Elderly Hospitalized Patients 
Research indicates that 40% of hospital-acquired delirium cases may be preventable. However, despite its clinical significance, delirium often goes unrecognized or is misdiagnosed. The purpose of this study was to assess the need for delirium education in acute care hospitals in Hamilton, Ontario.
Approximately 100 health professionals were trained as delirium screeners. On ‘Delirium Day’, all patients ≥ 65 years of age in non-critical care areas in all acute care sites in Hamilton were identified. Those willing to take part in the prevalence study were assessed for delirium using the Standardized Mini-Mental State Examination and the Confusion Assessment Method. The Research Ethics Boards at Hamilton Health Sciences and St. Joseph’s Healthcare Hamilton approved this quality assurance project.
Of the 562 patients eligible for screening, eight were excluded and six did not have sufficient data collected to assess for delirium. Of the 548 individuals screened for delirium, 10.6% screened positive. Prevalence estimates ranged by site from 0% to 21% and type of unit from 3.8% to 16%. Recognition of delirium by nursing staff was fair; but, documentation was usually absent.
While the prevalence rates were somewhat lower than in other studies, the results support the need for education among health-care providers in the prevention, identification, and management of delirium.
PMCID: PMC3516239  PMID: 23259011
delirium; elderly; acute care; education; healthcare providers
7.  Benzodiazepine and opioid use and the duration of ICU delirium in an older population 
Critical care medicine  2009;37(1):177-183.
There is a high prevalence of delirium in older medical intensive care unit (ICU) patients and delirium is associated with adverse outcomes. We need to identify modifiable risk factors for delirium in the ICU, such as medication use. The objective of this study was to examine the impact of benzodiazepine or opioid use on the duration of ICU delirium in an older medical population.
Prospective cohort study.
Fourteen-bed medical intensive care unit in an urban university teaching hospital.
304 consecutive admissions age 60 and older.
Main Outcome Measurements
The main outcome measure was duration of ICU delirium, specifically the first episode of ICU delirium. Patients were assessed daily for delirium with the Confusion Assessment Method for the ICU (CAM-ICU) and a validated chart review method. Our main predictor was the receipt of benzodiazepines or opioids during ICU stay. A multivariable model was developed using Poisson rate regression.
Delirium occurred in 239 of 304 patients (79%). The median duration of ICU delirium was 3 days with a range of 1-33 days. In a multivariable regression model receipt of a benzodiazepine or opioid (RR, 1.64, 95% CI, 1.27-2.10) was associated with increased delirium duration. Other variables associated with delirium duration in this analysis include preexisting dementia (RR, 1.19, 95% CI 1.07-1.33), receipt of haloperidol (RR, 1.35, 95% CI, 1.21-1.50), and severity of illness (RR, 1.01, 95% CI, 1.00-1.02).
The use of benzodiazepines or opioids in the ICU is associated with longer duration of a first episode of delirium. Receipt of these medications may represent modifiable risk factors for delirium. Clinicians caring for ICU patients should carefully evaluate the need for benzodiazepines, opioids and haloperidol.
PMCID: PMC2700732  PMID: 19050611
delirium; critical care; risk factors; aged; benzodiazepines; opioids; haloperidol
8.  Can an e-learning course improve nursing care for older people at risk of delirium: a stepped wedge cluster randomised trial 
BMC Geriatrics  2014;14:69.
Delirium occurs frequently in older hospitalised patients and is associated with several adverse outcomes. Ignorance among healthcare professionals and a failure to recognise patients suffering from delirium have been identified as the possible causes of poor care. The objective of the study was to determine whether e-learning can be an effective means of improving implementation of a quality improvement project in delirium care. This project aims primarily at improving the early recognition of older patients who are at risk of delirium.
In a stepped wedge cluster randomised trial an e-learning course on delirium was introduced, aimed at nursing staff. The trial was conducted on general medical and surgical wards from 18 Dutch hospitals. The primary outcome measure was the delirium risk screening conducted by nursing staff, measured through monthly patient record reviews. Patient records from patients aged 70 and over admitted onto wards participating in the study were used for data collection. Data was also collected on the level of delirium knowledge of these wards’ nursing staff.
Records from 1,862 older patients were included during the control phase and from 1,411 patients during the intervention phase. The e-learning course on delirium had a significant positive effect on the risk screening of older patients by nursing staff (OR 1.8, p-value <0.01), as well as on other aspects of delirium care. The number of patients diagnosed with delirium was reduced from 11.2% in the control phase to 8.7% in the intervention phase (p = 0.04). The e-learning course also showed a significant positive effect on nurses’ knowledge of delirium.
Nurses who undertook a delirium e-learning course showed a greater adherence to the quality improvement project in delirium care. This improved the recognition of patients at risk and demonstrated that e-learning can be a valuable instrument for hospitals when implementing improvements in delirium care.
Trial registration
The Netherlands National Trial Register (NTR). Trial number: NTR2885.
PMCID: PMC4046094  PMID: 24884739
Delirium; Education; Nurses; Quality improvement
9.  Delirium in the Emergency Department: an Independent Predictor of Death Within Six Months 
Annals of emergency medicine  2010;56(3):244-252.e1.
Delirium’s adverse effect on long-term mortality in older hospitalized patients is well documented, while its effect in older emergency department (ED) patients remains unclear. Similarly, the consequences of delirium on nursing home patients seen in the ED are also unknown. As a result, we sought to determine if delirium in the ED was independently associated with 6-month mortality in older patients and if this relationship was modified by nursing home status.
Our prospective cohort study was conducted at a tertiary care, academic ED using convenience sampling, and included English speaking patients who were 65 years and older and were in the ED for less than 12 hours at the time of enrollment. Patients were excluded if they refused consent, were previously enrolled, were unable to follow simple commands at baseline, were comatose, or had incomplete data. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) was used to determine delirium and was administered by trained research assistants. Cox proportional hazard regression was performed to determine if delirium in the ED was independently associated with 6-month mortality after adjusting for age, comorbidity burden, severity of illness, dementia, functional dependence, and nursing home residence. To test whether the effect of delirium in the ED on 6-month mortality was modified by nursing home residence, an interaction term (delirium*nursing home) was incorporated into the multivariable model. Hazard ratios (HR) with their 95% confidence intervals (95% CI) were reported.
Of the 628 patients enrolled, 108 (17.2%) were delirious in the ED and 58 (9.2%) were from the nursing home. For the entire cohort, the 6-month mortality rate was higher in the delirious group compared to the non-delirious group (37.0% versus 14.3%). Delirium was an independent predictor of increased 6-month mortality (HR = 1.72, 95% CI: 1.04 – 2.86) after adjusting for age, comorbidity burden, severity of illness, dementia, functional dependence, and nursing home residence. The “delirium*nursing home” interaction was non-significant (p=0.86), indicating that place of residence had no effect on the relationship between delirium in the ED and 6-month mortality.
Delirium in older ED patients is an independent predictor of increased 6-month mortality and this relationship appears to be present regardless of nursing home status.
PMCID: PMC3768121  PMID: 20363527
10.  Quantitative proteomics of delirium cerebrospinal fluid 
Translational Psychiatry  2014;4(11):e477-.
Delirium is a common cause and complication of hospitalization in older people, being associated with higher risk of future dementia and progression of existing dementia. However relatively little data are available on which biochemical pathways are dysregulated in the brain during delirium episodes, whether there are protein expression changes common among delirium subjects and whether there are any changes which correlate with the severity of delirium. We now present the first proteomic analysis of delirium cerebrospinal fluid (CSF), and one of few studies exploring protein expression changes in delirium. More than 270 proteins were identified in two delirium cohorts, 16 of which were dysregulated in at least 8 of 17 delirium subjects compared with a mild Alzheimer's disease neurological control group, and 31 proteins were significantly correlated with cognitive scores (mini-mental state exam and acute physiology and chronic health evaluation III). Bioinformatics analyses revealed expression changes in several protein family groups, including apolipoproteins, secretogranins/chromogranins, clotting/fibrinolysis factors, serine protease inhibitors and acute-phase response elements. These data not only provide confirmatory evidence that the inflammatory response is a component of delirium, but also reveal dysregulation of protein expression in a number of novel and unexpected clusters of proteins, in particular the granins. Another surprising outcome of this work is the level of similarity of CSF protein profiles in delirium patients, given the diversity of causes of this syndrome. These data provide additional elements for consideration in the pathophysiology of delirium as well as potential biomarker candidates for delirium diagnosis.
PMCID: PMC4259987  PMID: 25369144
11.  Prevalence and detection of delirium in elderly emergency department patients 
Delirium is a complex medical disorder associated with high morbidity and mortality among elderly patients. The goals of our study were to determine the prevalence of delirium in emergency department (ED) patients aged 65 years and over and to determine the sensitivity and specificity of a conventional clinical assessment by an ED physician for the detection of delirium in the same population.
All elderly patients presenting to the ED in a primary acute care, university-affiliated hospital who were triaged to the observation room on a stretcher because of the severity of their illness were screened for delirium by a research psychiatrist using the Mini-Mental State Examination and the Confusion Assessment Method. The diagnosis of "delirium" or an equivalent term by the ED physician was determined by 2 methods: completion of a mental status checklist by the ED physician and chart review. The prevalence of delirium and the sensitivity and specificity of the ED physician's clinical assessment were calculated with their 95% confidence intervals. The demographic and clinical characteristics of patients with detected delirium and those with undetected delirium were compared.
A sample of 447 patients was screened. The prevalence of delirium was 9.6% (95% confidence interval 6.9%-12.4%). The sensitivity of the detection of delirium by the ED physician was 35.3% and the specificity, 98.5%. Most patients with delirium had neurologic or pulmonary diseases, and most patients with detected delirium had neurologic diseases.
Despite the relatively high prevalence of delirium in elderly ED patients, the sensitivity of a conventional clinical assessment for this condition is low. There is a need to improve the detection of delirium by ED physician
PMCID: PMC80546  PMID: 11068569
12.  Pre- and Post-Transplantation Risk Factors for Delirium Onset and Severity in Patients Undergoing Hematopoietic Stem-Cell Transplantation 
Journal of Clinical Oncology  2011;29(7):895-901.
To determine pre- and post-transplantation risk factors for delirium onset and severity during the acute phase of myeloablative hematopoietic stem-cell transplantation (HSCT).
Patients and Methods
Ninety adult patients with malignancies admitted to the Fred Hutchinson Cancer Research Center for their first HSCT were assessed prospectively from 1 week before transplantation to 30 days after transplantation. Delirium was assessed three times per week using the Delirium Rating Scale and the Memorial Delirium Assessment Scale. Potential risk factors were assessed by patient self-report, charts, and computerized records. Multivariable analysis of time to onset of a delirium episode was undertaken using Cox proportional hazards regression with time-varying covariates. Analysis for delirium severity was carried out using a linear mixed effects model. Validation and sensitivity analyses were performed on the final models.
Forty-five patients (50%) experienced a delirium episode. Pretransplantation risk factors for onset and higher severity of delirium were higher mean alkaline phosphatase and blood urea nitrogen (BUN) levels. Poorer pretransplantation executive functioning was also associated with higher delirium severity. Higher doses of opioid medications were the only post-transplantation risk factor for delirium onset (hazard ratio, 1.05; 95% CI, 1.02 to 1.08). Higher opioid doses, current and prior pain, and higher BUN levels were post-transplantation risk factors for greater delirium severity (all P < .01).
Pre- and post-transplantation factors can assist in identifying patients who are at risk for delirium during myeloablative HSCT and may enable clinical interventions to prevent delirium onset or decrease delirium symptoms.
PMCID: PMC3068062  PMID: 21263081
13.  Reviewing the effect of nursing interventions on delirious patients admitted to intensive care unit of neurosurgery ward in Al-Zahra Hospital, Isfahan University of Medical Sciences 
Disease is an abnormal process that affects all aspects of the human life. The hospital environment and particularly the intensive care unit (ICU) causes stress in the patient and hi/her family. Delirium, due to its sudden onset and startle, unconsciousness, memory impairment, illusion and dynamic or sedentary behaviors, is known as one of the stressor agents. Despite its high prevalence and the high cost complications such as long term mechanical ventilation, hospital pneumonia, pressure ulcer, prolongation of hospitalization in the hospital or the intensive care units, performance reduction and increase in mortality, this disorder remains unknown in most cases. In line with the other treatment team members, nurses should also participate in controlling the discountable factors, helping patients to cope with uncontrollable factors and using pharmacological methods to manage the delirium and feature their own unique capacity more through quick recognition, reviewing the causes and providing scientific care in improving the quality of patient care and improving the patients’ health status. Hence, this study aimed to review the effect of nursing interventions on delirium of the patients admitted to ICU of the neurosurgery ward in Al-Zahra hospital in Isfahan.
A two-group multi-stage clinical trial study was carried out on 40 patients with hyperactive delirium admitted to ICU. The questionnaire included demographic data, Richmond Agitation Sedation Scale to assess the irritability rate and study method and also cognitive confusion in intensive care unit to determine delirium status of the study population. Simple sampling method was conducted and the study samples were randomly divided into two intervention and control groups. The following nursing interventions performed on the intervention group: assuring, emotional support, clear information and effective communication with the patients and their families and also allowing family visits twice a day. In the control group, the sample received the normal and routine ICU cares. The irritability and delirium severity status of the samples were analyzed on the day of admission and the fifth day using descriptive and inferential statistical methods and also SPSS software.
Statistical analysis showed that although there was no significant difference between the groups on the first day of admission in terms of the irritability and delirium severity status, this was significant on the fifth day of the study. Wilcoxon test in the intervention and control groups indicated a significant difference between the study subjects in terms of the irritability and delirium severity status on the first day of admission and the fifth day which indicated the reduction in the irritability severity. But, this reduction was higher in the intervention group than in the control group. Furthermore, McNemar test showed that the number of the subjects with delirium in both groups reduced on the fifth day compared to the first day of admission and there was a significant difference between these two days, the number of samples without delirium in the intervention group was almost two times higher than that in the control group on the fifth day.
Nursing interventions are considered as one of the non-pharmacological methods in treating delirium and by using these methods appropriately in ICUs, the patients’ hypoactive delirium can be reduced.
PMCID: PMC3203289  PMID: 22039387
Intensive care units; delirium; nursing interventions
14.  Pilot trial of Stop Delirium! (PiTStop) - a complex intervention to prevent delirium in care homes for older people: study protocol for a cluster randomised controlled trial 
Trials  2014;15:47.
Delirium (or acute confusion) is a serious illness common in older people, in which a person’s thinking and perceptions may be affected. Reducing delirium is important because of the considerable distress it causes, and the poor outcomes associated with it, such as increased admissions to hospital, falls, mortality and costs to the National Health Service (NHS). Preventing delirium is possible using multicomponent interventions; successful interventions in hospitals have reduced it by one-third. However, there is little research to guide practice in care homes, where it is common because of the clustering of known risk factors (older age, frailty, and dementia). In previous work we developed a multicomponent intervention to prevent delirium in care homes, called Stop Delirium! The intervention was based upon evidence from the research literature relating to the prevention of delirium and on strategies to change professional practice. Before starting a large costly trial of Stop Delirium!, this pilot study will test and help improve the design and feasibility of the trial protocol.
We plan to conduct a cluster randomised pilot trial in 14 care homes (independent residential and nursing). Following recruitment of residents (over 60 years, consenting or with consultee agreement, able to communicate in English, and not in palliative care) participating homes will be randomised, stratified by size of home and proportion of residents with dementia. Stop Delirium! will be delivered to intervention homes over 16 months, with controls receiving usual care. The primary outcome measure will be the presence of delirium on any day during a one-month post-intervention period.
We will collect data to determine 1) recruitment and attrition rates, 2) feasibility of various outcomes measurements, and 3) feasibility of capturing health resource use (resident diaries and by examining health records). We will estimate the between-cluster variation for the primary outcome, delirium occurrence.
This pilot study will refine methods for the definitive trial. The lessons learnt will also contribute to implementing National Institute for Health and Clinical Excellence (NICE) delirium guidelines, which recommend multicomponent interventions for delirium prevention.
Trial registration
PMCID: PMC3923732  PMID: 24495514
Pilot; Feasibility; RCT; Complex intervention; Older people; Delirium; Care home
15.  The Long-Term Effect of Delirium on the Cognitive Trajectory of Persons with Dementia 
Archives of internal medicine  2012;172(17):1324-1331.
Delirium is characterized by acute cognitive impairment. We examined the effect of delirium on long-term cognitive trajectory in older adults with Alzheimer's disease (AD).
Prospectively collected longitudinal data from a nested cohort of hospitalized patients with AD (n=263) in the Massachusetts Alzheimer's Disease Research Center Patient Registry during 1991–2006 (median follow-up: 3.2 years). Cognitive function was measured using the Information-Memory-Concentration (IMC) section of the Blessed Dementia Rating Scale. Delirium was identified using a validated chart review method. The pace of cognitive deterioration was contrasted using random effect regression models.
Over half of the sample of patients with AD developed delirium during hospitalization (56%). The pace of cognitive deterioration prior to hospitalization did not differ between patients who developed delirium (1.4 IMC points/year, 95% confidence interval, CI,0.7,2.1) and those who did not (0.8 IMC points/year, 95% CI: 0.3,1.3) (P=0.24). In the year following hospitalization, patients who had developed delirium experienced greater cognitive deterioration (3.1 IMC points/year, 95% CI: 2.1,4.1) relative to patients who did not develop delirium (1.4 IMC points/year, 95% CI: 0.2,2.6) after adjusting for confounders. The ratio of these changes suggests that following delirium, cognitive deterioration proceeds at 2.2 times the rate in patients without delirium in the year after hospitalization. The delirium group maintained a more rapid pace of cognitive deterioration throughout the 5-year period following hospitalization. Sensitivity analyses excluding rehospitalized patients and matching on baseline cognitive function and baseline pace of cognitive deterioration produced essentially identical results. The acceleration due to delirium was independent of dementia severity, comorbidity, and demographic characteristics.
Delirium is highly prevalent among persons with AD who are hospitalized and associated with an increased pace of cognitive deterioration which is maintained for up to 5 years. Strategies to prevent delirium may offer a promising avenue to explore for ameliorating cognitive deterioration in AD.
PMCID: PMC3740440  PMID: 23403619
16.  Delirium in Australian Hospitals: A Prospective Study 
Objectives. Australian data regarding delirium in older hospitalized patients are limited. Hence, this study aimed to determine the prevalence and incidence of delirium among older patients admitted to Australian hospitals and assess associated outcomes. Method. A prospective observational study (n = 493) of patients aged ≥70 years admitted to four Australian hospitals was undertaken. Trained research nurses completed comprehensive geriatric assessments using standardized instruments including the Confusion Assessment Method to assess for delirium. Nurses also visited the wards daily to assess for incident delirium and other adverse outcomes. Diagnoses of dementia and delirium were established through case reviews by independent physicians. Results. Overall, 9.7% of patients had delirium at admission and a further 7.6% developed delirium during the hospital stay. Dementia was the most important predictor of delirium at (OR = 3.18, 95% CI: 1.65–6.14) and during the admission (OR = 4.82; 95% CI: 2.19–10.62). Delirium at and during the admission predicted increased in-hospital mortality (OR = 5.19, 95% CI: 1.27–21.24; OR = 31.07, 95% CI: 9.30–103.78). Conclusion. These Australian data confirm that delirium is a common and serious condition among older hospital patients. Hospital clinicians should maintain a high index of suspicion for delirium in older patients.
PMCID: PMC3787633  PMID: 24151504
17.  Antipsychotic Use Among Nursing Home Residents Admitted with Hip Fracture 
Journal of the American Geriatrics Society  2012;61(1):10.1111/jgs.12043.
Widespread use of antipsychotic medications among skilled nursing home (NH) residents for off-label indications has become a concern of clinicians and policy makers. The objective of this study was to evaluate the association between receiving antipsychotics and the outcomes of a cohort of NH patients with and without presumed delirium after hip fracture.
Population based cohort study.
11,119 nursing homes nationwide, from 01 January 2000 to 31 December 2007.
First-time NH admits with hip fracture (N=77,759).
The Nursing Home Confusion Assessment Method was utilized to identify residents with no delirium, subsyndromal delirium, and full delirium. Propensity score reweighting was used with analyses stratified by delirium level.
Among patients with no delirium symptoms, about 5 percent (n = 3,250) received antipsychotic drugs. These individuals were less likely to be discharged home (OR 0.68; P < 0.001), had a higher likelihood of death prior to nursing home discharge (OR 1.28; P = 0.03), stayed in nursing homes longer (β 2.83; P = 0.05), and had less functional improvement at discharge (β -0.47; P = 0.03). Receipt of antipsychotics among participants with mild delirium was associated with a lower likelihood of discharge home (OR 0.74; P = 0.03).
Among NH residents with hip fracture and no delirium symptoms, use of antipsychotics was associated with worse outcomes, with the exception of rehospitalization. No clear benefits were associated with antipsychotic use for those with presumed delirium.
PMCID: PMC3854869  PMID: 23252409
Skilled Nursing Facility; Delirium; Antipsychotics
18.  Predisposing factors for delirium in the surgical intensive care unit 
Critical Care  2001;5(5):265-270.
Delirium is a sign of deterioration in the homeostasis and physical status of the patient. The objective of our study was to investigate the predisposing factors for delirium in a surgical intensive care unit (ICU) setting.
Between January 1996 and 1997, we screened prospectively 818 patients who were consecutive applicants to the general surgery service of Dicle-University Hospital and had been kept in the ICU for delirium. All patients were hospitalized either for elective or emergency services and were treated either with medication and/or surgery. Suspected cases of delirium were identified during daily interviews. The patients who had changes in the status of consciousness (n = 150) were consulted with an experienced consultation-liaison psychiatrist. The diagnosis of delirium was based on Diagnostic and Statistical Manual of Mental Disorders (revised third edition) criteria and established through psychiatric interviews. Patients were divided into two groups: the 'delirious group' (DG) (n = 90) and the 'non-delirious group' (NDG) (n = 728). During delirium, all abnormal findings related to physical conditions, laboratory features, and additional diseases were evaluated as probable risk factors of delirium.
Of 818 patients, 386 (47.2%) were male and 432 (52.8%) were female. Delirium developed in 90 of 818 patients (11%). The cases of delirium in the DG were more frequent among male patients (63.3%) than female patients (36.7%) (χ2 = 10.5, P = 0.001). The mean age was 48.9 ± 18.1 and 38.5 ± 13.8 years in the DG and NDG, respectively (t = 6.4, P = 0.000). Frequency of delirium is higher in the patients admitted to the Emergency Department (χ2 = 43.6, P = 0.000). The rate of postoperative delirium was 10.9%, but there was no statistical difference related to operations between the DG and NDG (χ2 = 0.13, P = 0.71). The length of stay in the ICU was 10.7 ± 13.9 and 5.6 ± 2.9 days in the DG and NDG, respectively (t = 0.11, P = 0.000). The length of stay in hospital was 15.6 ± 16.5 and 8.1 ± 2.7 days in the DG and NDG, respectively (t = 11.08, P = 0.000). Logistic regression was used to explore the associations between probable risk factors and delirium. Delirium was not correlated with conditions such as hypertension, hypo/hyperpotassemia, hypernatremia, hypoalbuminemia, hypo/hyperglycemia, cardiac disease, emergency admission, age, length of stay in the ICU, length of stay in hospital, and gender. It was determined that conditions such as respiratory diseases (odds ratio [OR] = 30.6, 95% confidence interval [CI] = 9.5–98.4), infections (OR = 18.0, 95% CI = 3.5–90.8), fever (OR = 14.3, 95% CI = 4.1–49.3), anemia (OR = 5.4, 95% CI = 1.6–17.8), hypotension (OR = 19.8, 95% CI = 5.3–74.3), hypocalcemia (OR = 30.9, 95% CI = 5.8–163.2), hyponatremia (OR = 8.2, 95% CI = 2.5–26.4), azotemia (OR = 4.6, 95% CI = 1.4–15.6), elevated liver enzymes (OR = 6.3, 95% CI = 1.2–32.2), hyperamylasemia (OR = 43.4, 95% CI = 4.2–442.7), hyperbilirubinemia (OR = 8.7, 95% CI = 2.0–37.7) and metabolic acidosis (OR = 4.5, 95% CI = 1.1–17.7) were predicting factors for delirium.
We determined that conditions such as respiratory diseases, infections, fever, anemia, hypotension, hypocalcemia, hyponatremia, azotemia, elevated liver enzymes, hyperamylasemia, hyperbilirubinemia and metabolic acidosis were predicting factors for delirium.
PMCID: PMC83853  PMID: 11737901
delirium; intensive care unit; predisposing factors
The Journal of trauma  2008;65(1):34-41.
Delirium or acute brain dysfunction is extremely prevalent in medical intensive care unit (ICU) patients, but limited data exist regarding its prevalence and risk factors among surgical (SICU) and trauma ICU (TICU) patients. The purpose of this study was to determine the prevalence and risk factors for delirium in surgical and trauma ICU patients.
SICU and TICU patients requiring mechanical ventilation (MV) >24 hours were prospectively evaluated for delirium using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method for the ICU (CAM-ICU). Those with baseline dementia, intracranial injury, or ischemic/hemorrhagic strokes that would confound the evaluation of delirium were excluded. Markov models were used to determine predictors for daily transition to delirium.
One-hundred patients (46 SICU and 54 TICU) were enrolled. Prevalence of delirium was 73% in the SICU and 67% in the TICU. Multivariable analyses identified midazolam [OR 2.75 (CI 1.43–5.26, p = 0.002)] exposure as the strongest independent risk factor for transitioning to delirium. Opiate exposure showed an inconsistent message such that fentanyl was a risk factor for delirium in the SICU (p = 0.007) but not in the TICU (p = 0.936), while morphine exposure was associated with a lower risk of delirium (SICU, p = 0.069; TICU p = 0.024).
Approximately 7 out of 10 SICU and TICU patients experience delirium. In keeping with other recent data on benzodiazepines, exposure to midazolam is an independent and potentially modifiable risk factor for the transitioning to delirium.
PMCID: PMC3773485  PMID: 18580517
trauma; surgery; cognitive impairment; delirium; mechanical ventilation; critical care; sedatives and analgesic
20.  Frequency, Risk Factors, and Prognosis of Prolonged Delirium in Elderly Patients After Hip Fracture Surgery 
Delirium in elderly patients after hip fracture surgery is believed to be a transient event, although it frequently lasts for more than 4 weeks.
We determined the incidence, risk factors, morbidity, and mortality of prolonged delirium in elderly patients after hip fracture surgery.
Patients and Methods
We evaluated 232 elderly patients (older than 65 years) (232 hips) who underwent hip fracture surgery for the development and duration of delirium and categorized them into three groups; nondelirium group, transient (≤ 4 weeks) delirium group, and prolonged (> 4 weeks) delirium group. Patients underwent a global geriatric evaluation, which included postoperative complications, mortality, and functional and mental status evaluations. The three groups were compared with respect to these variables.
Seventy patients (30.2%) had delirium develop, and among these, 14 (20%) had prolonged delirium with a total incidence of 6%. Multivariate analysis showed preinjury dementia was a risk factor of prolonged delirium. At the final followup, five (62.5%) of the eight patients who were ambulatory outdoors in the prolonged delirium group became housebound, whereas only 18 (16.4%) of the 110 patients who were ambulatory outdoors in the nondelirium group became housebound. Survival at 40 months was 81.0% (95% confidence interval, 72.6%–89.3%) in the nondelirium group and 63.6% (95% confidence interval, 35.2%–92.1%) in the prolonged delirium group.
Prolonged delirium was found to be associated with a poor functional outcome and increased mortality.
Level of Evidence
Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC3148394  PMID: 21327416
21.  Risk factors for incident delirium among older people in acute hospital medical units: a systematic review and meta-analysis 
Age and Ageing  2014;43(3):326-333.
Background: delirium affects up to 40% of older hospitalised patients, but there has been no systematic review focussing on risk factors for incident delirium in older medical inpatients. We aimed to synthesise data on risk factors for incident delirium and where possible conduct meta-analysis of these.
Methods: PubMed and Web of Science databases were searched (January 1987–August 2013). Studies were quality rated using the Newcastle-Ottawa Scale. We used the Mantel–Haenszel and inverse variance method to estimate the pooled odds ratio (OR) or mean difference for individual risk factors.
Results: eleven articles met inclusion criteria and were included for review. Total study population 2338 (411 patients with delirium/1927 controls). The commonest factors significantly associated with delirium were dementia, older age, co-morbid illness, severity of medical illness, infection, ‘high-risk’ medication use, diminished activities of daily living, immobility, sensory impairment, urinary catheterisation, urea and electrolyte imbalance and malnutrition. In pooled analyses, dementia (OR 6.62; 95% CI (confidence interval) 4.30, 10.19), illness severity (APACHE II) (MD (mean difference) 3.91; 95% CI 2.22, 5.59), visual impairment (OR 1.89; 95% CI 1.03, 3.47), urinary catheterisation (OR 3.16; 95% CI 1.26, 7.92), low albumin level (MD −3.14; 95% CI −5.99, −0.29) and length of hospital stay (OR 4.85; 95% CI 2.20, 7.50) were statistically significantly associated with delirium.
Conclusion: we identified risk factors consistently associated with incident delirium following admission. These factors help to highlight older acute medical inpatients at risk of developing delirium during their hospital stay.
PMCID: PMC4001175  PMID: 24610863
delirium; risk factors; older people; hospitalised; medical unit
22.  Managing delirium in the acute care setting: a pilot focus group study 
Delirium frequently occurs in hospitalised older adults leading to poor outcomes and frequent adverse events. Proper recognition and management of delirium by acute care nurses can minimise the effects of negative sequelae associated with delirium.
This pilot study used focus group methodology to: (i) describe acute care nurse’s experience and knowledge regarding assessment and management of delirium in hospitalised older adults; (ii) illustrate potential facilitators and barriers to non-drug management of delirium; and (iii) to explicate the use of non-drug interventions by acute care nurses to manage delirium in hospitalised older adults.
Qualitative, pilot study.
A total of 16 nurse participants, working on medical, surgical and orthopaedic units from one acute care hospital participated in two focus groups.
Main themes included the following: confusion is normal; our duty is to protect; and finding a balance. Nurses were able to identify non-pharmacological interventions for delirium and facilitators and barriers to using these in clinical practice.
Findings from this pilot study illustrate the need for regular assessment of cognitive status in hospitalised older adults and nursing staff education regarding the use of non-pharmacological management of delirium. Based on their experience, nurses have a wealth of ideas for managing delirium. Areas for future research and policy are also highlighted.
Implications for practice
More research is needed on how to improve delirium management by acute care nurses to increase the efficacy and use of non-pharmacological interventions in the management of delirium in hospitalised older adults. To translate these findings into practice, nursing care needs to be guided by evidence-based guidelines to implement non-pharmacological strategies in the acute care setting.
PMCID: PMC3555484  PMID: 22513181
acute care system; cognitive impairment; dementia; older people nursing
23.  Predicting Delirium Duration in Elderly Hip-Surgery Patients: Does Early Symptom Profile Matter? 
Background. Features that may allow early identification of patients at risk of prolonged delirium, and therefore of poorer outcomes, are not well understood. The aim of this study was to determine if preoperative delirium risk factors and delirium symptoms (at onset and clinical symptomatology during the course of delirium) are associated with delirium duration. Methods. This study was conducted in prospectively identified cases of incident delirium. We compared patients experiencing delirium of short duration (1 or 2 days) with patients who had more prolonged delirium (≥3 days) with regard to DRS-R-98 (Delirium Rating Scale Revised-98) symptoms on the first delirious day. Delirium symptom profile was evaluated daily during the delirium course. Results. In a homogenous population of 51 elderly hip-surgery patients, we found that the severity of individual delirium symptoms on the first day of delirium was not associated with duration of delirium. Preexisting cognitive decline was associated with prolonged delirium. Longitudinal analysis using the generalised estimating equations method (GEE) identified that more severe impairment of long-term memory across the whole delirium episode was associated with longer duration of delirium. Conclusion. Preexisting cognitive decline rather than severity of individual delirium symptoms at onset is strongly associated with delirium duration.
PMCID: PMC3600209  PMID: 23533395
24.  Delirium as a predictor of sepsis in post-coronary artery bypass grafting patients: a retrospective cohort study 
Critical Care  2010;14(5):R171.
Delirium is the most common neurological complication following cardiac surgery. Much research has focused on potential causes of delirium; however, the sequelae of delirium have not been well investigated. The objective of this study was to investigate the relationship between delirium and sepsis post coronary artery bypass grafting (CABG) and to determine if delirium is a predictor of sepsis.
Peri-operative data were collected prospectively on all patients. Subjects were identified as having agitated delirium if they experienced a short-term mental disturbance marked by confusion, illusions and cerebral excitement. Patient characteristics were compared between those who became delirious and those who did not. The primary outcome of interest was post-operative sepsis. The association of delirium with sepsis was assessed by logistic regression, adjusting for differences in age, acuity, and co-morbidities.
Among 14,301 patients, 981 became delirious and 227 developed sepsis post-operatively. Rates of delirium increased over the years of the study from 4.8 to 8.0% (P = 0.0003). A total of 70 patients of the 227 with sepsis, were delirious. In 30.8% of patients delirium preceded the development of overt sepsis by at least 48 hours. Multivariate analysis identified several factors associated with sepsis, (receiver operating characteristic (ROC) 79.3%): delirium (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6 to 3.4), emergent surgery (OR 3.3, CI 2.2 to 5.1), age (OR 1.2, CI 1.0 to 1.3), pre-operative length of stay (LOS) more than seven days (OR 1.6, CI 1.1 to 2.3), pre-operative renal insufficiency (OR 1.9, CI 1.2 to 2.9) and complex coronary disease (OR 3.1, CI 1.8 to 5.3).
These data demonstrate an association between delirium and post-operative sepsis in the CABG population. Delirium emerged as an independent predictor of sepsis, along with traditional risk factors including age, pre-operative renal failure and peripheral vascular disease. Given the advancing age and increasing rates of delirium in the CABG population, the prevention and management of delirium need to be addressed.
PMCID: PMC3219273  PMID: 20875113
25.  New horizons in the pathogenesis, assessment and management of delirium 
Age and Ageing  2013;42(6):667-674.
Delirium is one of the foremost unmet medical needs in healthcare. It affects one in eight hospitalised patients and is associated with multiple adverse outcomes including increased length of stay, new institutionalisation, and considerable patient distress. Recent studies also show that delirium strongly predicts future new-onset dementia, as well as accelerating existing dementia. The importance of delirium is now increasingly being recognised, with a growing research base, new professional international organisations, increased interest from policymakers, and greater prominence of delirium in educational and audit programmes. Nevertheless, the field faces several complex research and clinical challenges. In this article we focus on selected areas of recent progress and/or uncertainty in delirium research and practice. (i) Pathogenesis: recent studies in animal models using peripheral inflammatory stimuli have begun to suggest mechanisms underlying the delirium syndrome as well as its link with dementia. A growing body of blood and cerebrospinal fluid studies in humans have implicated inflammatory and stress mediators. (ii) Prevention: delirium prevention is effective in the context of research studies, but there are several unresolved issues, including what components should be included, the role of prophylactic drugs, and the overlap with general best care for hospitalised older people. (iii) Assessment: though there are several instruments for delirium screening and assessment, detection rates remain dismal. There are no clear solutions but routine screening embedded into clinical practice, and the development of new rapid screening instruments, offer potential. (iv) Management: studies are difficult given the heterogeneity of delirium and currently expert and comprehensive clinical care remains the main recommendation. Future studies may address the role of drugs for specific elements of delirium. In summary, though facing many challenges, the field continues to make progress, with several promising lines of enquiry and an expanding base of interest among researchers, clinicians and policymakers.
PMCID: PMC3809721  PMID: 24067500
delirium; older people; delirium pathogenesis; delirium assessment; delirium management

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