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Delirium in Elderly Patients and the Risk of Postdischarge Mortality, Institutionalization, and Dementia:  A Meta-analysis FREE

Joost Witlox, MSc; Lisa S. M. Eurelings, MSc; Jos F. M. de Jonghe, PhD; Kees J. Kalisvaart, MD, PhD; Piet Eikelenboom, MD, PhD; Willem A. van Gool, MD, PhD
[+] Author Affiliations

Author Affiliations: Department of Geriatric Medicine, Medical Center Alkmaar, Alkmaar, the Netherlands (Mr Witlox and Dr de Jonghe); Department of Neurology, Academic Medical Center, Amsterdam, the Netherlands (Ms Eurelings and Drs Eikelenboom and van Gool); Department of Geriatric Medicine, Kennemer Gasthuis, Haarlem, the Netherlands (Dr Kalisvaart); and GGZinGeest, Amsterdam, the Netherlands (Dr Eikelenboom).


JAMA. 2010;304(4):443-451. doi:10.1001/jama.2010.1013.
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Context Delirium is a common and serious complication in elderly patients. Evidence suggests that delirium is associated with long-term poor outcome but delirium often occurs in individuals with more severe underlying disease.

Objective To assess the association between delirium in elderly patients and long-term poor outcome, defined as mortality, institutionalization, or dementia, while controlling for important confounders.

Data Sources A systematic search of studies published between January 1981 and April 2010 was conducted using the databases of MEDLINE, EMBASE, PsycINFO, and CINAHL.

Study Selection Observational studies of elderly patients with delirium as a study variable and data on mortality, institutionalization, or dementia after a minimum follow-up of 3 months, and published in the English or Dutch language. Titles, abstracts, and articles were reviewed independently by 2 of the authors. Of 2939 references in the original search, 51 relevant articles were identified.

Data Extraction Information on study design, characteristics of the study population, and outcome were extracted. Quality of studies was assessed based on elements of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies.

Data Synthesis The primary analyses included only high-quality studies with statistical control for age, sex, comorbid illness or illness severity, and baseline dementia. Pooled-effect estimates were calculated with random-effects models. The primary analysis with adjusted hazard ratios (HRs) showed that delirium is associated with an increased risk of death compared with controls after an average follow-up of 22.7 months (7 studies; 271/714 patients [38.0%] with delirium, 616/2243 controls [27.5%]; HR, 1.95 [95% confidence interval {CI}, 1.51-2.52]; I2, 44.0%). Moreover, patients who had experienced delirium were also at increased risk of institutionalization (7 studies; average follow-up, 14.6 months; 176/527 patients [33.4%] with delirium and 219/2052 controls [10.7%]; odds ratio [OR], 2.41 [95% CI, 1.77-3.29]; I2, 0%) and dementia (2 studies; average follow-up, 4.1 years; 35/56 patients [62.5%] with delirium and 15/185 controls [8.1%]; OR, 12.52 [95% CI, 1.86-84.21]; I2, 52.4%). The sensitivity, trim-and-fill, and secondary analyses with unadjusted high-quality risk estimates stratified according to the study characteristics confirmed the robustness of these results.

Conclusion This meta-analysis provides evidence that delirium in elderly patients is associated with poor outcome independent of important confounders, such as age, sex, comorbid illness or illness severity, and baseline dementia.

Figures in this Article

Delirium is a syndrome of acutely altered mental status characterized by inattention and a fluctuating course.1 With occurrence rates of up to half of older patients postoperatively, and even higher in elderly patients admitted to intensive care units, delirium is the most common complication in hospitalized older people.24 Delirium causes distress to patients and caregivers, has been associated with increased morbidity and mortality, and is a major burden to health care services in terms of expenditures.5

Numerous studies have addressed the long-term prognosis of older individuals who experienced delirium during hospitalization. The evidence that these studies provide is not entirely consistent (eg, older patients with delirium experienced increased long-term mortality in one study,6 but not in another7). Elements of study design, such as delirium and outcome ascertainment and time to follow-up, may affect conclusions. Whether delirium independently contributes to poor outcome or merely represents a marker of underlying disease is especially relevant. The long-term detrimental sequelae of delirium are difficult to disentangle from the effects of specific characteristics of the study population, such as the extent of medical illness and the presence or absence of dementia.

These issues preclude drawing reliable conclusions regarding the long-term prognosis after delirium, which could be instrumental in assessing the value of prevention and treatment8 and in counseling patients and caregivers. Therefore, we systematically reviewed and summarized data regarding the risk of long-term poor outcome (defined as mortality, institutionalization, or dementia) after delirium. Our main objective was to assess the association between delirium and long-term poor outcomes in elderly patients while controlling for important confounders.

We followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines.9 We conducted a comprehensive literature search of MEDLINE, EMBASE, PsycINFO, and CINAHL databases for studies published between January 1981 and April 2010. We started our search in January 1981 because a formal nomenclature that differentiates delirium from dementia was first established with the Diagnostic and Statistical Manual of Mental Disorders (Third Edition) in 1980.10 Search key words for delirium (ie, delirium, confusion, acute confusional state, acute confusional syndrome) were cross-referenced to citations pertinent to outcome (ie, mortality, prognos*, predict*, course). Studies that met each of the following criteria were considered eligible: (1) mean or median age of the study population of 65 years or older; (2) delirium as a study variable; (3) presentation of quantitative data (ie, event rates, odds ratios [ORs] or hazard ratios [HRs]) reflecting the association between delirium and outcome (ie, mortality, institutionalization, or dementia); (4) hospital or postacute care setting; and (5) follow-up assessment at 3 months or later. Searches were restricted to articles published in the English or Dutch language. Articles were excluded if they recruited (1) delirium patients only and no controls; (2) homogeneous populations of terminally ill patients (eg, patients with end-stage cancer); and (3) homogeneous populations of patients with central nervous system disease (eg, only patients with stroke or Parkinson disease). After exclusion of case studies and case series, the database searches identified 2939 articles. Reviews were hand searched for additional references but yielded no additional articles. Title and abstract review of all articles was completed by 3 of the authors (J.W., L.S.M.E., W.A.vG.). Full reports of 162 potentially relevant articles were independently reviewed by at least 2 investigators (J.W., L.S.M.E., W.A.vG.) to establish eligibility according to the inclusion criteria.

A standardized, piloted data extraction form was used for recording information. Data extraction was completed by 3 of the authors (J.W., L.S.M.E., W.A.vG.) using the following approach. For the primary analyses, we obtained statistically adjusted ORs and HRs with corresponding 95% confidence intervals (CIs) and noted the type of statistical adjustment (ie, the variables that were examined as possible covariates in relation with the outcomes of interest). For the secondary analyses, we extracted the number of events relative to the total number of participants in the delirium and control groups (ie, event rates). Because of our interest in the long-term outcomes after delirium, we preferentially extracted event rates that considered only postdischarge mortality and incident cases of institutionalization (or dementia). Therefore, if specified, event rates for mortality were corrected for death during the index hospitalization and event rates for institutionalization (and dementia) were corrected for baseline rates of institutionalization (or dementia).

Study populations were characterized as surgical, medical, or mixed and the following information was recorded: primary author, publication year, country of origin, study design, criteria for delirium and dementia ascertainment, duration of follow-up, average or median age, and (if applicable) the proportion of in-hospital mortality, baseline institutionalization, and dementia. Additional information such as separate event rates for patients with and without dementia were requested from 33 authors and 26 authors responded. Disagreement between reviewers during the selection and extraction process was resolved through consensus.

To limit heterogeneity resulting from differences in study design, we only included high-quality articles in the primary and secondary analyses. Lesser-quality articles were not included in any of our analyses. The quality of the studies was assessed based on elements from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies.11 High-quality articles were defined as studies that diagnosed delirium prospectively, as opposed to, for example, retrospective chart review, and used a validated method for delirium ascertainment.

Studies were included in the primary analyses only if adequate statistical control was provided to account for the effect of important covariates on the association between delirium and poor outcome. Adequate adjustment was defined as statistical control for the covariables of age, sex, comorbid illness or illness severity, and baseline dementia. We selected these variables because they are risk factors for delirium in elderly patients that can themselves be associated independently with poor outcome.2,5

Secondary analyses were performed on a much larger sample of studies to examine the robustness of results from our primary analyses. In these secondary analyses, the studies' unadjusted ORs were stratified according to source of the study population, age (<80 years vs ≥80 years), country of origin (United States vs Europe), length of follow-up, and whether individuals who were institutionalized or had dementia were included in the study population.

Finally, an exploratory secondary analysis was conducted to specifically examine the association of baseline dementia with the long-term prognosis after delirium. This analysis was performed using studies that allowed separate calculation of effect estimates among homogeneous populations of individuals with and without dementia.

Mortality, institutionalization, and dementia were examined as separate outcomes. In primary analyses, we pooled adjusted ORs and HRs across all studies based on the extracted risk estimates and corresponding 95% CIs. In secondary analyses, we combined ORs and 95% CIs that we recalculated based on event rates in the delirium and control groups.12 If recalculation was not possible, the reported unadjusted ORs and 95% CIs were used.

Each study contributed only 1 effect size per analysis. If data were duplicated between studies, the largest study was used. If studies reported data on several follow-up assessments, we included only data from the latest follow-up. If necessary, different subgroups (eg, based on age) were combined to create 1 estimate per study.

The pooled ORs and HRs were calculated as the weighted average and weighting was assigned according to the inverse of the variance. An OR or HR greater than 1 indicates an increased risk of an outcome among delirium patients compared with controls. The I2 statistic was used to examine the heterogeneity of effect sizes in the overall aggregations. The I2 values of 25% or less indicate low heterogeneity, values near 50% indicate moderate heterogeneity, and values near 75% or greater indicate high heterogeneity.13 Unless otherwise specified, random-effects models were used in all analyses.14 Fixed-effects models were only used in sensitivity analyses that examined if these models yielded similar results.

Publication bias was evaluated with a combination of 2 funnel plot–based methods: the Egger regression asymmetry test15 to investigate funnel plot asymmetry and the trim-and-fill method16 to estimate the number of missing studies and to calculate a corrected OR as if these studies were present. Because 5 studies are usually too few to detect an asymmetrical funnel, only aggregated analyses with more than 5 studies were subjected to trim-and-fill analysis.17 The effect of potential outliers was examined by comparing the pooled estimate with estimates obtained after iterations using k − 1 findings. Studies were treated as statistical outliers when the k − 1 estimate produced a 95% CI that did not overlap with the 95% CI of the aggregated estimate.

Sensitivity analyses were performed on our primary and secondary data sets to examine if risk estimates using postdischarge mortality only (excluding in-hospital or postacute care deaths) provided a more conservative estimate of the association between delirium and mortality and if the strength of the relationship between delirium and institutionalization was affected by including only risk estimates that were based on incident cases of institutionalization. Furthermore, we performed a sensitivity analysis to examine if studies that used different methods to diagnose baseline dementia (eg, chart review) and incident dementia at follow-up (eg, cognitive testing) overestimated the association between delirium and dementia. Studies with the same method to diagnose dementia at baseline and follow-up and that thus included only incident cases of dementia were pooled in these analyses.

Statistical analyses were performed using Comprehensive Meta-Analysis software (Englewood, New Jersey) version 2.2.048. P values of less than .05 were considered statistically significant.

Our literature search yielded 2939 articles, of which we identified 162 for further review. Fifty-one studies met our inclusion criteria (see eTable 1, eTable 2, and eTable 3). Most excluded studies lacked either follow-up assessment, sufficient data to extract a risk estimate, a control group, or original data. Of the 51 studies that met our inclusion criteria, 9 studies1826 did not satisfy our quality criteria and were not included in the primary or secondary analyses (Figure 1).

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Figure 1. Identification, Review, and Selection of Articles Included in the Meta-analysis
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Of the remaining 42 high-quality studies,6,7,2766 23 studies6,7,2730,32,34,35,40,41,44,45,48,51,52,55,56,60,61,6365 reported statistically adjusted effect estimates for the outcome of mortality and 16 studies6,7,27,29,30,32,35,40,41,45,48,51,52,60,63,65 fulfilled criteria for adequate adjustment. Four studies27,29,30,48 did not report sufficient information to extract an adjusted risk estimate for the latest follow-up assessment. The remaining 12 studies6,7,32,35,40,41,45,51,52,60,63,65 provided 7 HRs and 7 ORs for the primary analysis of the association between delirium and mortality. Eight studies6,7,30,32,40,43,61,63 reported adjusted ORs for the association between delirium and institutionalization, of which 7 studies6,7,30,32,40,43,63 were adequately adjusted and provided 9 ORs for the primary analysis. Three studies presented adjusted ORs for the dementia outcome, of which 2 studies32,54 were adequately adjusted and their ORs are included in our primary analysis.

For the secondary analyses with unadjusted ORs, 38 studies6,7,27,29,3137,3956,5866 provided 40 ORs on mortality, 18 studies6,7,30,32,33,37,40,42,43,46,47,49,55,57,6163,66 provided 20 ORs on institutionalization, and 6 studies32,41,47,49,54,65 provided 6 ORs on dementia. In 2 instances, ORs were recalculated based on the data supplied by the authors because nursing home residents had been excluded6,63 and data had been provided on a substantially larger sample.48 Four sets of studies2830,38,52,54,57 reported data on the same group of patients; the studies that reported postdischarge mortality54 or presented data of the largest sample29,30,52 were included.

In our exploratory secondary analyses, we examined to what extent baseline dementia affected the association between delirium and poor outcome. A total of 18 studies6,27,28,35,3739,41,43,45,4749,59,62,63,65,66 provided 18 ORs on mortality and 5 ORs on institutionalization in a homogeneous population of individuals with dementia, and 17 ORs on mortality and 6 ORs on institutionalization in a homogeneous population of individuals without dementia. Descriptive information regarding the studies that were included from each analysis is listed in eTables 1-3 and information on excluded studies is listed in eTable 4.

Mortality

The primary analysis of adequately adjusted HRs included a total of 2957 participants. After a mean (SD) follow-up of 22.7 (15.5) months (range, 3-48 months) in 7 studies, 271 of 714 patients with delirium (38%) had an increased risk of death compared with 616 of 2243 controls (27.5%) (HR, 1.95 [95% CI, 1.51-2.52]; I2, 44.0%; Figure 2). There was no evidence of publication bias according to the Egger regression asymmetry test (β = 0.16; P = .94) or the trim-and-fill method and outliers were not identified. The aggregated analysis of adequately adjusted ORs included a total of 2066 participants and also showed a significant association between delirium and mortality after a mean (SD) follow-up of 11.4 (14.0) months (range, 3-38 months) in 183 of 483 participants with delirium (37.9%) vs 316 of 1583 controls (20.0%) (OR, 1.71 [95% CI, 1.27-2.30]; I2, 0%). No evidence of publication bias (Egger β = −0.37; P = .43) or outliers was found.

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Figure 2. Primary Analyses
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Analyses of the association between delirium and mortality, institutionalization, and dementia adjusted for age, sex, comorbid illness or illness severity, and baseline dementia. CI indicates confidence interval. Weighting was assigned according to the inverse of the variance. Hazard ratios and odds ratios larger than 1 indicate increased risk of mortality, institutionalization, or dementia among participants who experienced delirium.

A sensitivity analysis with adjusted HRs showed that the association between delirium and death remained significant when only studies for which postdischarge mortality could be determined were included (Table 1). Secondary analyses with unadjusted ORs (see the eFigure) were consistent with the results of the primary analyses. Additional stratified analyses with these unadjusted data revealed that excess mortality was present among patients who had experienced delirium regardless of the source of the study population, inclusion of nursing home residents or individuals with dementia, age, country of origin, and follow-up time (see eTable 5).

Table Graphic Jump LocationTable 1. Primary Analyses of the Association Between Delirium and Mortality, Institutionalization, and Dementia in Studies Adjusted for Age, Sex, Comorbid Illness or Illness Severity, and Baseline Dementia

Our exploratory secondary analysis showed that the association of delirium with mortality persisted independent of preexisting dementia. Delirium remained significantly associated with mortality when 222 of 643 patients with delirium superimposed on dementia (34.5%) were compared with 135 of 564 patients with dementia only (23.9%) (OR, 1.75 [95% CI, 1.30-2.36]; I2, 0.7%), and when 168 of 575 patients with delirium only (29.2%) were compared with 266 of 1620 patients with neither delirium nor dementia (16.4%) (OR, 2.36 [95% CI, 1.82-3.05]; I2, 2.1%; Table 2).

Table Graphic Jump LocationTable 2. Primary Risk-Adjusted Analyses and Secondary Unadjusted Analyses
Institutionalization

The primary analysis of adjusted ORs included 2579 participants in 7 studies. Delirium was associated with an increased risk of institutionalization after a mean (SD) follow-up of 14.6 (12.0) months (range, 3-38 months) in 176 of 527 participants with delirium (33.4%) vs 219 of 2052 controls (10.7%) (OR, 2.41 [95% CI, 1.77-3.29]; I2, 0%; (Figure 2). No evidence of publication bias was identified using the Egger regression asymmetry test (β = 0.45; P = .65) but the trim-and-filled method simulated 1 missing study (OR, 2.32 [95% CI, 1.69-3.21]). No evidence of outliers was found. A sensitivity analysis showed that the association between delirium and institutionalization remained when only cases who had not resided in an institution at baseline were considered (Table 1).

Secondary analyses with unadjusted ORs produced similar results (see the eFigure). Additional stratified analyses with unadjusted ORs showed that higher rates of institutionalization were present among individuals who experienced delirium regardless of the source of the study population (ie, inclusion of individuals with dementia, age, country of origin, and follow-up time; see eTable 5).

Our exploratory secondary analyses showed that delirium remained significantly associated with institutionalization when 80 of 174 patients with delirium superimposed on dementia (46.0%) were compared with 42 of 208 patients with dementia only (20.2%) (OR, 2.55 [95% CI, 1.56-4.18]; I2, 0%), but the association was not significant when 24 of 108 patients with delirium only (22.2%) were compared with 29 of 237 patients with neither delirium nor dementia (12.2%) (OR, 3.25 [95% CI, 0.85-12.45]; I2, 66.5%), although the number of patients in these study categories were small and power was limited (Table 2).

Dementia

The primary analysis of adequately adjusted ORs summarized the results of 2 studies and included 241 participants. Thirty-five of 56 patients with delirium (62.5%) had an increased risk of dementia at follow-up compared with 15 of 185 controls (8.1%) after 3.2 and 5.0 years of follow-up (OR, 12.52 [95% CI, 1.86-84.21]; I2, 52.4%; Figure 2). Because only 2 studies were available for this primary analysis of adjusted risk estimates, no sensitivity or trim-and-fill analyses were performed. The secondary analysis confirmed the results of the primary analysis and showed that the association remained significant when only incident cases of dementia (from studies that had the same method of ascertainment at baseline and follow-up) were included (see eTable 5).

The results of this meta-analysis provide evidence that delirium in elderly patients is associated with an increased risk of death, institutionalization, and dementia, independent of age, sex, comorbid illness or illness severity, and presence of dementia at baseline. Moreover, our stratified models confirm that this association persists when excluding studies that included in-hospital deaths and patients residing in an institution at baseline.

The results of this meta-analysis can be instrumental in patient care. The low rate of survival and the high rates of institutionalization and dementia indicate that older people who experience delirium should be considered an especially vulnerable population (see Figure 3 and Table 2). The results of this meta-analysis gain special clinical relevance considering that delirium in some cases can be prevented.8 However, once delirium is present, management of delirium has not been found to improve long-term mortality or need for institutional care.67 Thus, identifying patients at high risk for delirium and implementing strategies aimed at preventing delirium may help to avert some of the delirium–associated poor outcomes these patients experience.

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Figure 3. Meta-analytic Survival Curve
Graphic Jump Location

Based on mortality rates among patients that experienced delirium during hospitalization from studies listed in the eFigure. Circles are proportional to study size and depict the proportion of surviving individuals. For specified periods, aggregated weighted estimates for survival are depicted by a horizontal line with corresponding 95% confidence intervals (gray area). For example, 2 to 4 years after delirium, 45% of individuals are still alive.

This, to our knowledge, is the first study to systematically summarize the risk of poor outcome in elderly patients who experienced delirium. We used a comprehensive search strategy and systematic review method, following recommendations from the MOOSE guidelines.9 In our meta-analysis, we limited heterogeneity and potential sources of bias by including only high-quality studies in elderly patients in the hospital or postacute care settings, excluding population studies. We identified high-quality studies using individual methodological aspects because summary scores to identify trials of high quality can be problematic.68 Furthermore, our approach subdivided poor outcome into several categories, thereby avoiding potential heterogeneity that may arise when a single summary estimate is used. Our primary analyses controlled for selected covariates that may influence the association between delirium and poor outcome. We also performed secondary analyses of unadjusted effect estimates and demonstrated that the associations persisted regardless of the study population, the inclusion of nursing home residents or patients with dementia, age, country of origin, and time of follow-up. Heterogeneity, potential outliers, and publication bias were examined and were not responsible for the associations identified.

There are several methodological limitations to our study. Given the nature of delirium, all studies in our meta-analysis are observational; diverse study designs and patient characteristics make interpretation of aggregated estimates challenging and causality cannot be inferred.9 Nevertheless, delirium was associated with poor outcomes even after controlling for important covariates. Moreover, heterogeneity was low to moderate in the analyses of longer-term outcomes, suggesting that variations in findings are compatible with chance alone and not likely to be caused by genuine differences between studies.13

In our meta-analysis, studies were pooled irrespective of their definition of delirium. In most studies, delirium was diagnosed by experts based on criteria derived from the Diagnostic and Statistical Manual of Mental Disorders1,10,69,70; thus, broadly similar methods were used. With regard to the ascertainment of dementia, more variety was present. For instance, because of the high prevalence of delirium at hospital admission,71 evaluation of cognitive function based on patient interviews may have overestimated the number of participants with preexisting dementia. Although no significant heterogeneity emerged when we pooled studies that adopted alternative definitions of delirium or dementia, differences in case ascertainment may have introduced some random error.

Only a small number of studies examined the risk of dementia after delirium. Importantly, sensitivity analyses restricted to incident cases of dementia yielded somewhat more conservative estimates of the association between delirium and dementia. Only 1 study54 provided an adjusted OR based on incident cases, so no meta-analysis could be performed in this most stringent subgroup.

We restricted our search to English- and Dutch-language sources and we did not search gray literature or blind the data abstractors to the data sources. However, we believe that the magnitude and consistency of the observed effects render an important effect of bias unlikely in this respect. Moreover, we rigorously controlled for publication bias and used random-effects models that are generally better suited when studies are only gathered from the published literature.14

Several important clinical findings emerge from our meta-analysis. The persistence of the association between delirium and poor outcome years after the occurrence of delirium and presumably resolution of the precipitating factors suggests that delirium is not merely a marker of underlying disease. This is substantiated by our finding that the increased risk of poor outcome after delirium cannot readily be explained by predisposing factors, such as age, sex, comorbid illness or illness severity, and presence of baseline dementia. Moreover, the results of our stratified analyses suggest that even patients without the given risk factor analyzed experience adverse outcomes after delirium at least as often as do those with the risk factor. This somewhat counterintuitive finding may be because for vulnerable (eg, older, cognitively impaired) patients, relatively mild precipitating factors suffice to precipitate delirium, whereas in relatively healthier patients, a greater insult is required,72 and those kinds of insults may be associated with a poorer long-term prognosis. Alternatively, the long-term detrimental effects of delirium in vulnerable populations may compete with other risks for poor outcome. Furthermore, delirium may be more difficult to detect in patients with dementia, resulting in misclassification and bias toward the null.

A number of potential explanations for the observed association between delirium and poor outcome can be hypothesized. Delirium may persist and a protracted course of delirium may contribute to increased morbidity and complications, exemplified by the association between delirium and the new concept of postoperative cognitive dysfunction.73 In turn, the increased morbidity and complications may lead to poor outcome.74 Persistence of symptoms can also be an indication that the underlying medical illness is still active or has deteriorated during the follow-up period. Alternatively, the factors that precipitated delirium may incite a detrimental sequence of events in the brain. Through overactivation of microglia and an aberrant stress response, the resulting uncontrolled neuroinflammation, elevation of cortisol levels, and neurotransmitter imbalances can persist for months, reducing the threshold for new episodes of delirium and potentially causing prolongation of neuropsychiatric symptoms.75,76

Delirium is a serious and common neuropsychiatric syndrome that may markedly affect outcome and long-term prognosis of elderly patients. Future studies will have to establish what exact mechanisms are responsible for the long-term poor outcomes after delirium and whether clinical characteristics of delirium itself (eg, duration or subtype) differentially influence prognosis. Moreover, clinical trials are needed to investigate whether the long-term sequelae associated with delirium can be averted.

Corresponding Author: Willem A. van Gool, MD, PhD, Department of Neurology, Academic Medical Center, PO Box 22700, 1100 DE Amsterdam, the Netherlands (w.a.vangool@amc.uva.nl).

Authors Contributions: Mr Witlox had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: van Gool, Witlox.

Acquisition of data: Witlox, Eurelings.

Analysis and interpretation of data: van Gool, Witlox, Eurelings, Eikelenboom, de Jonghe, Kalisvaart.

Drafting of the manuscript: Witlox, van Gool.

Critical revision of the manuscript for important intellectual content: van Gool, Witlox, Eikelenboom, de Jonghe, Eurelings, Kalisvaart.

Statistical analysis: Witlox, van Gool.

Administrative, technical, or material support: Witlox, van Gool, Eurelings.

Study supervision: van Gool, Eikelenboom, de Jonghe, Kalisvaart.

Financial Disclosures: None reported.

Additional Contributions: We thank all investigators for supplying additional information for this meta-analysis and particularly the following investigators: Giuseppe Bellelli, MD (Department of Rehabilitation and Aged Care, Ancelle Della Carità Hospital, Brescia, Italy), Jim George, MD (North Cumbria University Hospitals, Carlisle, England), Frederick Sieber, MD (Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland), Koen Milisen, PhD (Center for Health Services and Nursing Research, Catholic University Leuven, Leuven, Belgium; Division of Geriatric Medicine, Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium), Melissa Andrew, MD (Division of Geriatric Medicine, Dalhousie University, Halifax, Nova Scotia, Canada), Andrea Giusti, MD (Department of Gerontology, Galliera Hospital, Genova, Italy), Barbara van Munster, MD, PhD (Department of Medicine, Academic Medical Centre, University of Amsterdam), Ritz Kakuma, PhD (Health Systems Research and Consulting Unit, Centre for Addiction and Mental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada), Dimitrios Adamis, MD (Consultant in Old Age Psychiatry, Research and Academic Institute of Athens, Greece), Birgitta Olofsson, PhD (Department of Nursing, Umeå University, Umeå, Sweden), Horst Bickel, PhD (Department of Psychiatry and Psychotherapy, Technischen Universität München, München, Germany), L. Joseph Melton III, MD, PhD (College of Medicine, Mayo Clinic, Rochester, Minnesota), Kaisu Pitkälä, MD, PhD (Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland), and Gianluca Isaia, MD (Department of Medical and Surgical Disciplines, Geriatric Section, San Giovanni Battista Hospital, University of Torino, Italy). No compensation was given to any of these investigators for supplying additional information to us.

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Sutton AJ, Duval SJ, Tweedie RL,  et al.  Empirical assessment of effect of publication bias on meta-analyses.  BMJ. 2000;320(7249):1574-1577
PubMed   |  Link to Article
Dolan MM, Hawkes WG, Zimmerman SI,  et al.  Delirium on hospital admission in aged hip fracture patients.  J Gerontol A Biol Sci Med Sci. 2000;55(9):M527-M534
PubMed   |  Link to Article
Harjola VP, Follath F, Nieminen MS,  et al.  Characteristics, outcomes, and predictors of mortality at 3 months and 1 year in patients hospitalized for acute heart failure.  Eur J Heart Fail. 2010;12(3):239-248
PubMed   |  Link to Article
Heijmeriks JA, Dassen W, Prenger K, Wellens HJ. The incidence and consequences of mental disturbances in elderly patients post cardiac surgery.  Clin Cardiol. 2000;23(7):540-546
PubMed   |  Link to Article
Iwata M, Kuzuya M, Kitagawa Y,  et al.  Underappreciated predictors for postdischarge mortality in acute hospitalized oldest-old patients.  Gerontology. 2006;52(2):92-98
PubMed   |  Link to Article
Loponen P, Luther M, Wistbacka JO,  et al.  Postoperative delirium and health related quality of life after coronary artery bypass grafting.  Scand Cardiovasc J. 2008;42(5):337-344
PubMed   |  Link to Article
Poór G, Atkinson EJ, O’Fallon WM, Melton LJ III. Determinants of reduced survival following hip fractures in men.  Clin Orthop Relat Res. 1995;(319):260-265
PubMed
Rudolph JL, Marcantonio ER, Culley DJ,  et al.  Delirium is associated with early postoperative cognitive dysfunction.  Anaesthesia. 2008;63(9):941-947
PubMed   |  Link to Article
Satish S, Winograd CH, Chavez C, Bloch DA. Geriatric targeting criteria as predictors of survival and health care utilization.  J Am Geriatr Soc. 1996;44(8):914-921
PubMed
Wacker P, Nunes PV, Cabrita H, Forlenza OV. Post-operative delirium is associated with poor cognitive outcome and dementia.  Dement Geriatr Cogn Disord. 2006;21(4):221-227
PubMed   |  Link to Article
Adamis D, Treloar A, Darwiche FZ,  et al.  Associations of delirium with in-hospital and in 6-months mortality in elderly medical inpatients.  Age Ageing. 2007;36(6):644-649
PubMed   |  Link to Article
Bellelli G, Frisoni GB, Turco R,  et al.  Delirium superimposed on dementia predicts 12-month survival in elderly patients discharged from a postacute rehabilitation facility.  J Gerontol A Biol Sci Med Sci. 2007;62(11):1306-1309
PubMed   |  Link to Article
Bellelli G, Morghen S, Turco R, Trabucchi M. Delirium in older people.  Age Ageing. 2008;37(3):353-354
PubMed   |  Link to Article
Bellelli G, Magnifico F, Trabucchi M. Outcomes at 12 months in a population of elderly patients discharged from a rehabilitation unit.  J Am Med Dir Assoc. 2008;9(1):55-64
PubMed   |  Link to Article
Berggren D, Gustafson Y, Eriksson B,  et al.  Postoperative confusion after anesthesia in elderly patients with femoral neck fractures.  Anesth Analg. 1987;66(6):497-504
PubMed   |  Link to Article
Bickel H, Gradinger R, Kochs E, Förstl H. High risk of cognitive and functional decline after postoperative delirium.  Dement Geriatr Cogn Disord. 2008;26(1):26-31
PubMed   |  Link to Article
Brännström B, Gustafson Y, Norberg A, Winblad B. Problems of basic nursing care in acutely confused and non-confused hip-fracture patients.  Scand J Caring Sci. 1989;3(1):27-34
PubMed   |  Link to Article
Curyto KJ, Johnson J, TenHave T,  et al.  Survival of hospitalized elderly patients with delirium.  Am J Geriatr Psychiatry. 2001;9(2):141-147
PubMed
de Rooij SE, Buurman BM, Korevaar JC,  et al.  Co-morbidity in acutely hospitalised older patients as a risk factor for death in hospital or within 3 months after discharge [in Dutch].  Ned Tijdschr Geneeskd. 2007;151(36):1987-1993
PubMed
Edelstein DM, Aharonoff GB, Karp A,  et al.  Effect of postoperative delirium on outcome after hip fracture.  Clin Orthop Relat Res. 2004;(422):195-200
PubMed
Edlund A, Lundström M, Lundström G,  et al.  Clinical profile of delirium in patients treated for femoral neck fractures.  Dement Geriatr Cogn Disord. 1999;10(5):325-329
PubMed   |  Link to Article
Edlund A, Lundström M, Brännström B,  et al.  Delirium before and after operation for femoral neck fracture.  J Am Geriatr Soc. 2001;49(10):1335-1340
PubMed   |  Link to Article
Edlund A, Lundström M, Karlsson S,  et al.  Delirium in older patients admitted to general internal medicine.  J Geriatr Psychiatry Neurol. 2006;19(2):83-90
PubMed   |  Link to Article
Francis J, Kapoor WN. Prognosis after hospital discharge of older medical patients with delirium.  J Am Geriatr Soc. 1992;40(6):601-606
PubMed
Furlaneto ME, Garcez-Leme LE. Impact of delirium on mortality and cognitive and functional performance among elderly people with femoral fractures.  Clinics (Sao Paulo). 2007;62(5):545-552
PubMed   |  Link to Article
George J, Bleasdale S, Singleton SJ. Causes and prognosis of delirium in elderly patients admitted to a district general hospital.  Age Ageing. 1997;26(6):423-427
PubMed   |  Link to Article
Giusti A, Barone A, Oliveri M,  et al.  An analysis of the feasibility of home rehabilitation among elderly people with proximal femoral fractures.  Arch Phys Med Rehabil. 2006;87(6):826-831
PubMed   |  Link to Article
González M, de Pablo J, Valdés M,  et al.  Delirium.  Eur J Psychiatry. 2005;19(3):165-171
González M, Martínez G, Calderón J,  et al.  Impact of delirium on short-term mortality in elderly inpatients.  Psychosomatics. 2009;50(3):234-238
PubMed   |  Link to Article
Gustafson Y, Berggren D, Brännström B,  et al.  Acute confusional states in elderly patients treated for femoral neck fracture.  J Am Geriatr Soc. 1988;36(6):525-530
PubMed
Isaia G, Astengo MA, Tibaldi V,  et al.  Delirium in elderly home-treated patients.  Age (Dordr). 2009;31(2):109-117
PubMed   |  Link to Article
Kakuma R, du Fort GG, Arsenault L,  et al.  Delirium in older emergency department patients discharged home.  J Am Geriatr Soc. 2003;51(4):443-450
PubMed   |  Link to Article
Kat MG, Vreeswijk R, de Jonghe JF,  et al.  Long-term cognitive outcome of delirium in elderly hip surgery patients.  Dement Geriatr Cogn Disord. 2008;26(1):1-8
PubMed   |  Link to Article
Koster S, Hensens AG, van der Palen J. The long-term cognitive and functional outcomes of postoperative delirium after cardiac surgery.  Ann Thorac Surg. 2009;87(5):1469-1474
PubMed   |  Link to Article
Levkoff SE, Evans DA, Liptzin B,  et al.  Delirium.  Arch Intern Med. 1992;152(2):334-340
PubMed   |  Link to Article
Leslie DL, Zhang Y, Holford TR,  et al.  Premature death associated with delirium at 1-year follow-up.  Arch Intern Med. 2005;165(14):1657-1662
PubMed   |  Link to Article
Lewis LM, Miller DK, Morley JE,  et al.  Unrecognized delirium in ED geriatric patients.  Am J Emerg Med. 1995;13(2):142-145
PubMed   |  Link to Article
Lundström M, Edlund A, Bucht G,  et al.  Dementia after delirium in patients with femoral neck fractures.  J Am Geriatr Soc. 2003;51(7):1002-1006
PubMed   |  Link to Article
Marcantonio ER, Flacker JM, Michaels M, Resnick NM. Delirium is independently associated with poor functional recovery after hip fracture.  J Am Geriatr Soc. 2000;48(6):618-624
PubMed
Marcantonio ER, Kiely DK, Simon SE,  et al.  Outcomes of older people admitted to postacute facilities with delirium.  J Am Geriatr Soc. 2005;53(6):963-969
PubMed   |  Link to Article
McAvay GJ, Van Ness PH, Bogardus ST Jr,  et al.  Older adults discharged from the hospital with delirium.  J Am Geriatr Soc. 2006;54(8):1245-1250
PubMed   |  Link to Article
Minden SL, Carbone LA, Barsky A,  et al.  Predictors and outcomes of delirium.  Gen Hosp Psychiatry. 2005;27(3):209-214
PubMed   |  Link to Article
Milisen K, Foreman MD, Abraham IL,  et al.  A nurse-led interdisciplinary intervention program for delirium in elderly hip-fracture patients.  J Am Geriatr Soc. 2001;49(5):523-532
PubMed   |  Link to Article
Nightingale S, Holmes J, Mason J, House A. Psychiatric illness and mortality after hip fracture.  Lancet. 2001;357(9264):1264-1265
PubMed   |  Link to Article
O’Keeffe S, Lavan J. The prognostic significance of delirium in older hospital patients.  J Am Geriatr Soc. 1997;45(2):174-178
PubMed
Olofsson B, Lundström M, Borssén B,  et al.  Delirium is associated with poor rehabilitation outcome in elderly patients treated for femoral neck fractures.  Scand J Caring Sci. 2005;19(2):119-127
PubMed   |  Link to Article
Pitkala KH, Laurila JV, Strandberg TE, Tilvis RS. Prognostic significance of delirium in frail older people.  Dement Geriatr Cogn Disord. 2005;19(2-3):158-163
PubMed   |  Link to Article
Pompei P, Foreman M, Rudberg MA,  et al.  Delirium in hospitalized older persons.  J Am Geriatr Soc. 1994;42(8):809-815
PubMed
Rockwood K, Cosway S, Carver D,  et al.  The risk of dementia and death after delirium.  Age Ageing. 1999;28(6):551-556
PubMed   |  Link to Article
Zakriya K, Sieber FE, Christmas C,  et al.  Brief postoperative delirium in hip fracture patients affects functional outcome at three months.  Anesth Analg. 2004;98(6):1798-1802
PubMed   |  Link to Article
Pitkälä KH, Laurila JV, Strandberg TE, Tilvis RS. Multicomponent geriatric intervention for elderly inpatients with delirium.  J Gerontol A Biol Sci Med Sci. 2006;61(2):176-181
PubMed   |  Link to Article
Jüni P, Witschi A, Bloch R, Egger M. The hazards of scoring the quality of clinical trials for meta-analysis.  JAMA. 1999;282(11):1054-1060
PubMed   |  Link to Article
American Psychiatric Association.  Diagnostic and Statistical Manual of Mental Disorders. 3rd ed, revised. Washington, DC: American Psychiatric Association; 1987
American Psychiatric Association.  Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994
Juliebø V, Bjøro K, Krogseth M,  et al.  Risk factors for preoperative and postoperative delirium in elderly patients with hip fracture.  J Am Geriatr Soc. 2009;57(8):1354-1361
PubMed   |  Link to Article
Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons.  JAMA. 1996;275(11):852-857
PubMed   |  Link to Article
Moller JT, Cluitmans P, Rasmussen LS,  et al; ISPOCD Investigators.  Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study.  Lancet. 1998;351(9106):857-861
PubMed   |  Link to Article
Cole MG, Ciampi A, Belzile E, Zhong L. Persistent delirium in older hospital patients.  Age Ageing. 2009;38(1):19-26
PubMed   |  Link to Article
van Gool WA, van de Beek D, Eikelenboom P. Systemic infection and delirium.  Lancet. 2010;375(9716):773-775
PubMed   |  Link to Article
Maclullich AM, Ferguson KJ, Miller T,  et al.  Unravelling the pathophysiology of delirium.  J Psychosom Res. 2008;65(3):229-238
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure 1. Identification, Review, and Selection of Articles Included in the Meta-analysis
Graphic Jump Location
Place holder to copy figure label and caption
Figure 2. Primary Analyses
Graphic Jump Location

Analyses of the association between delirium and mortality, institutionalization, and dementia adjusted for age, sex, comorbid illness or illness severity, and baseline dementia. CI indicates confidence interval. Weighting was assigned according to the inverse of the variance. Hazard ratios and odds ratios larger than 1 indicate increased risk of mortality, institutionalization, or dementia among participants who experienced delirium.

Place holder to copy figure label and caption
Figure 3. Meta-analytic Survival Curve
Graphic Jump Location

Based on mortality rates among patients that experienced delirium during hospitalization from studies listed in the eFigure. Circles are proportional to study size and depict the proportion of surviving individuals. For specified periods, aggregated weighted estimates for survival are depicted by a horizontal line with corresponding 95% confidence intervals (gray area). For example, 2 to 4 years after delirium, 45% of individuals are still alive.

Tables

Table Graphic Jump LocationTable 1. Primary Analyses of the Association Between Delirium and Mortality, Institutionalization, and Dementia in Studies Adjusted for Age, Sex, Comorbid Illness or Illness Severity, and Baseline Dementia
Table Graphic Jump LocationTable 2. Primary Risk-Adjusted Analyses and Secondary Unadjusted Analyses

References

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PubMed   |  Link to Article
Dolan MM, Hawkes WG, Zimmerman SI,  et al.  Delirium on hospital admission in aged hip fracture patients.  J Gerontol A Biol Sci Med Sci. 2000;55(9):M527-M534
PubMed   |  Link to Article
Harjola VP, Follath F, Nieminen MS,  et al.  Characteristics, outcomes, and predictors of mortality at 3 months and 1 year in patients hospitalized for acute heart failure.  Eur J Heart Fail. 2010;12(3):239-248
PubMed   |  Link to Article
Heijmeriks JA, Dassen W, Prenger K, Wellens HJ. The incidence and consequences of mental disturbances in elderly patients post cardiac surgery.  Clin Cardiol. 2000;23(7):540-546
PubMed   |  Link to Article
Iwata M, Kuzuya M, Kitagawa Y,  et al.  Underappreciated predictors for postdischarge mortality in acute hospitalized oldest-old patients.  Gerontology. 2006;52(2):92-98
PubMed   |  Link to Article
Loponen P, Luther M, Wistbacka JO,  et al.  Postoperative delirium and health related quality of life after coronary artery bypass grafting.  Scand Cardiovasc J. 2008;42(5):337-344
PubMed   |  Link to Article
Poór G, Atkinson EJ, O’Fallon WM, Melton LJ III. Determinants of reduced survival following hip fractures in men.  Clin Orthop Relat Res. 1995;(319):260-265
PubMed
Rudolph JL, Marcantonio ER, Culley DJ,  et al.  Delirium is associated with early postoperative cognitive dysfunction.  Anaesthesia. 2008;63(9):941-947
PubMed   |  Link to Article
Satish S, Winograd CH, Chavez C, Bloch DA. Geriatric targeting criteria as predictors of survival and health care utilization.  J Am Geriatr Soc. 1996;44(8):914-921
PubMed
Wacker P, Nunes PV, Cabrita H, Forlenza OV. Post-operative delirium is associated with poor cognitive outcome and dementia.  Dement Geriatr Cogn Disord. 2006;21(4):221-227
PubMed   |  Link to Article
Adamis D, Treloar A, Darwiche FZ,  et al.  Associations of delirium with in-hospital and in 6-months mortality in elderly medical inpatients.  Age Ageing. 2007;36(6):644-649
PubMed   |  Link to Article
Bellelli G, Frisoni GB, Turco R,  et al.  Delirium superimposed on dementia predicts 12-month survival in elderly patients discharged from a postacute rehabilitation facility.  J Gerontol A Biol Sci Med Sci. 2007;62(11):1306-1309
PubMed   |  Link to Article
Bellelli G, Morghen S, Turco R, Trabucchi M. Delirium in older people.  Age Ageing. 2008;37(3):353-354
PubMed   |  Link to Article
Bellelli G, Magnifico F, Trabucchi M. Outcomes at 12 months in a population of elderly patients discharged from a rehabilitation unit.  J Am Med Dir Assoc. 2008;9(1):55-64
PubMed   |  Link to Article
Berggren D, Gustafson Y, Eriksson B,  et al.  Postoperative confusion after anesthesia in elderly patients with femoral neck fractures.  Anesth Analg. 1987;66(6):497-504
PubMed   |  Link to Article
Bickel H, Gradinger R, Kochs E, Förstl H. High risk of cognitive and functional decline after postoperative delirium.  Dement Geriatr Cogn Disord. 2008;26(1):26-31
PubMed   |  Link to Article
Brännström B, Gustafson Y, Norberg A, Winblad B. Problems of basic nursing care in acutely confused and non-confused hip-fracture patients.  Scand J Caring Sci. 1989;3(1):27-34
PubMed   |  Link to Article
Curyto KJ, Johnson J, TenHave T,  et al.  Survival of hospitalized elderly patients with delirium.  Am J Geriatr Psychiatry. 2001;9(2):141-147
PubMed
de Rooij SE, Buurman BM, Korevaar JC,  et al.  Co-morbidity in acutely hospitalised older patients as a risk factor for death in hospital or within 3 months after discharge [in Dutch].  Ned Tijdschr Geneeskd. 2007;151(36):1987-1993
PubMed
Edelstein DM, Aharonoff GB, Karp A,  et al.  Effect of postoperative delirium on outcome after hip fracture.  Clin Orthop Relat Res. 2004;(422):195-200
PubMed
Edlund A, Lundström M, Lundström G,  et al.  Clinical profile of delirium in patients treated for femoral neck fractures.  Dement Geriatr Cogn Disord. 1999;10(5):325-329
PubMed   |  Link to Article
Edlund A, Lundström M, Brännström B,  et al.  Delirium before and after operation for femoral neck fracture.  J Am Geriatr Soc. 2001;49(10):1335-1340
PubMed   |  Link to Article
Edlund A, Lundström M, Karlsson S,  et al.  Delirium in older patients admitted to general internal medicine.  J Geriatr Psychiatry Neurol. 2006;19(2):83-90
PubMed   |  Link to Article
Francis J, Kapoor WN. Prognosis after hospital discharge of older medical patients with delirium.  J Am Geriatr Soc. 1992;40(6):601-606
PubMed
Furlaneto ME, Garcez-Leme LE. Impact of delirium on mortality and cognitive and functional performance among elderly people with femoral fractures.  Clinics (Sao Paulo). 2007;62(5):545-552
PubMed   |  Link to Article
George J, Bleasdale S, Singleton SJ. Causes and prognosis of delirium in elderly patients admitted to a district general hospital.  Age Ageing. 1997;26(6):423-427
PubMed   |  Link to Article
Giusti A, Barone A, Oliveri M,  et al.  An analysis of the feasibility of home rehabilitation among elderly people with proximal femoral fractures.  Arch Phys Med Rehabil. 2006;87(6):826-831
PubMed   |  Link to Article
González M, de Pablo J, Valdés M,  et al.  Delirium.  Eur J Psychiatry. 2005;19(3):165-171
González M, Martínez G, Calderón J,  et al.  Impact of delirium on short-term mortality in elderly inpatients.  Psychosomatics. 2009;50(3):234-238
PubMed   |  Link to Article
Gustafson Y, Berggren D, Brännström B,  et al.  Acute confusional states in elderly patients treated for femoral neck fracture.  J Am Geriatr Soc. 1988;36(6):525-530
PubMed
Isaia G, Astengo MA, Tibaldi V,  et al.  Delirium in elderly home-treated patients.  Age (Dordr). 2009;31(2):109-117
PubMed   |  Link to Article
Kakuma R, du Fort GG, Arsenault L,  et al.  Delirium in older emergency department patients discharged home.  J Am Geriatr Soc. 2003;51(4):443-450
PubMed   |  Link to Article
Kat MG, Vreeswijk R, de Jonghe JF,  et al.  Long-term cognitive outcome of delirium in elderly hip surgery patients.  Dement Geriatr Cogn Disord. 2008;26(1):1-8
PubMed   |  Link to Article
Koster S, Hensens AG, van der Palen J. The long-term cognitive and functional outcomes of postoperative delirium after cardiac surgery.  Ann Thorac Surg. 2009;87(5):1469-1474
PubMed   |  Link to Article
Levkoff SE, Evans DA, Liptzin B,  et al.  Delirium.  Arch Intern Med. 1992;152(2):334-340
PubMed   |  Link to Article
Leslie DL, Zhang Y, Holford TR,  et al.  Premature death associated with delirium at 1-year follow-up.  Arch Intern Med. 2005;165(14):1657-1662
PubMed   |  Link to Article
Lewis LM, Miller DK, Morley JE,  et al.  Unrecognized delirium in ED geriatric patients.  Am J Emerg Med. 1995;13(2):142-145
PubMed   |  Link to Article
Lundström M, Edlund A, Bucht G,  et al.  Dementia after delirium in patients with femoral neck fractures.  J Am Geriatr Soc. 2003;51(7):1002-1006
PubMed   |  Link to Article
Marcantonio ER, Flacker JM, Michaels M, Resnick NM. Delirium is independently associated with poor functional recovery after hip fracture.  J Am Geriatr Soc. 2000;48(6):618-624
PubMed
Marcantonio ER, Kiely DK, Simon SE,  et al.  Outcomes of older people admitted to postacute facilities with delirium.  J Am Geriatr Soc. 2005;53(6):963-969
PubMed   |  Link to Article
McAvay GJ, Van Ness PH, Bogardus ST Jr,  et al.  Older adults discharged from the hospital with delirium.  J Am Geriatr Soc. 2006;54(8):1245-1250
PubMed   |  Link to Article
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