Protocol for the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) study: a pragmatic, randomised clinical trial.

INTRODUCTION: Postoperative delirium, arbitrarily defined as occurring within 5 days of surgery, affects up to 50% of patients older than 60 after a major operation. This geriatric syndrome is associated with longer intensive care unit and hospital stay, readmission, persistent cognitive deterioration and mortality. No effective preventive methods have been identified, but preliminary evidence suggests that EEG monitoring during general anaesthesia, by facilitating reduced anaesthetic exposure and EEG suppression, might decrease incident postoperative delirium. This study hypothesises that EEG-guidance of anaesthetic administration prevents postoperative delirium and downstream sequelae, including falls and decreased quality of life. METHODS AND ANALYSIS: This is a 1232 patient, block-randomised, double-blinded, comparative effectiveness trial. Patients older than 60, undergoing volatile agent-based general anaesthesia for major surgery, are eligible. Patients are randomised to 1 of 2 anaesthetic approaches. One group receives general anaesthesia with clinicians blinded to EEG monitoring. The other group receives EEG-guidance of anaesthetic agent administration. The outcomes of postoperative delirium (≤5 days), falls at 1 and 12 months and health-related quality of life at 1 and 12 months will be compared between groups. Postoperative delirium is assessed with the confusion assessment method, falls with ProFaNE consensus questions and quality of life with the Veteran's RAND 12-item Health Survey. The intention-to-treat principle will be followed for all analyses. Differences between groups will be presented with 95% CIs and will be considered statistically significant at a two-sided p<0.05. ETHICS AND DISSEMINATION: Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) is approved by the ethics board at Washington University. Recruitment began in January 2015. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media. TRIAL REGISTRATION NUMBER: NCT02241655; Pre-results.

Delirium accelerates cognitive decline in Alzheimer disease.

OBJECTIVE: To examine the impact of delirium on the trajectory of cognitive function in a cohort of patients with Alzheimer disease (AD). METHODS: A secondary analysis of data collected from a large prospective cohort, the Massachusetts Alzheimer's Disease Research Center's patient registry, examined cognitive performance over time in patients who developed (n = 72) or did not develop (n = 336) delirium during the course of their illnesses. Cognitive performance was measured by change in score on the Information-Memory-Concentration (IMC) subtest of the Blessed Dementia Rating Scale. Delirium was identified using a previously validated chart review method. Using linear mixed regression models, rates of cognitive change were calculated, controlling for age, sex, education, comorbid medical diagnoses, family history of dementia, dementia severity score, and duration of symptoms before diagnosis. RESULTS: A significant acceleration in the slope of cognitive decline occurs following an episode of delirium. Among patients who developed delirium, the average decline at baseline for performance on the IMC was 2.5 points per year, but after an episode of delirium there was further decline to an average of 4.9 points per year (p = 0.001). Across groups, the rate of change in IMC score occurred about three times faster in those who had delirium compared to those who did not. CONCLUSIONS: Delirium can accelerate the trajectory of cognitive decline in patients with Alzheimer disease (AD). The information from this study provides the foundation for future randomized intervention studies to determine whether prevention of delirium might ameliorate or delay cognitive decline in patients with AD.

Delirium is associated with early postoperative cognitive dysfunction.

The purpose of this analysis was to determine if postoperative delirium was associated with early postoperative cognitive dysfunction (at 7 days) and long-term postoperative cognitive dysfunction (at 3 months). The International Study of Postoperative Cognitive Dysfunction recruited 1218 subjects >or= 60 years old undergoing elective, non-cardiac surgery. Postoperatively, subjects were evaluated for delirium using the criteria of the Diagnostic and Statistical Manual. Subjects underwent neuropsychological testing pre-operatively and postoperatively at 7 days (n = 1018) and 3 months (n = 946). Postoperative cognitive dysfunction was defined as a composite Z-score > 2 across tests or at least two individual test Z-scores > 2. Subjects with delirium were significantly less likely to participate in postoperative testing. Delirium was associated with an increased incidence of early postoperative cognitive dysfunction (adjusted risk ratio 1.6, 95% CI 1.1-2.1), but not long-term postoperative cognitive dysfunction (adjusted risk ratio 1.3, 95% CI 0.6-2.4). Delirium was associated with early postoperative cognitive dysfunction, but the relationship of delirium to long-term postoperative cognitive dysfunction remains unclear.

Nurses' recognition of delirium and its symptoms: comparison of nurse and researcher ratings.

BACKGROUND: Nurses play a key role in recognition of delirium, yet delirium is often unrecognized by nurses. Our goals were to compare nurse ratings for delirium using the Confusion Assessment Method based on routine clinical observations with researcher ratings based on cognitive testing and to identify factors associated with underrecognition by nurses. METHODS: In a prospective study, 797 patients 70 years and older underwent 2721 paired delirium ratings by nurses and researchers. Patient-related factors associated with underrecognition of delirium by nurses were examined. RESULTS: Delirium occurred in 239 (9%) of 2721 observations or 131 (16%) of 797 patients. Nurses identified delirium in only 19% of observations and 31% of patients compared with researchers. Sensitivities of nurses' ratings for delirium and its key features were generally low (15%-31%); however, specificities were high (91%-99%). Nearly all disagreements between nurse and researcher ratings were because of underrecognition of delirium by the nurses. Four independent risk factors for underrecognition by nurses were identified: hypoactive delirium (adjusted odds ratio [OR], 7.4; 95% confidence interval [CI], 4.2-12.9), age 80 years and older (OR, 2.8; 95% CI, 1.7-4.7), vision impairment (OR, 2.2; 95% CI, 1.2-4.0), and dementia (OR, 2.1; 95% CI, 1.2-3.7). The risk for underrecognition by nurses increased with the number of risk factors present from 2% (0 risk factors) to 6% (1 risk factor), 15% (2 risk factors), and 44% (3 or 4 risk factors; P(trend)<.001). Patients with 3 or 4 risk factors had a 20-fold risk for underrecognition of delirium by nurses. CONCLUSIONS: Nurses often missed delirium when present, but rarely identified delirium when absent. Recognition of delirium can be enhanced with education of nurses in delirium features, cognitive assessment, and factors associated with poor recognition.

Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU).

CONTEXT: Delirium is a common problem in the intensive care unit (ICU). Accurate diagnosis is limited by the difficulty of communicating with mechanically ventilated patients and by lack of a validated delirium instrument for use in the ICU. OBJECTIVES: To validate a delirium assessment instrument that uses standardized nonverbal assessments for mechanically ventilated patients and to determine the occurrence rate of delirium in such patients. DESIGN AND SETTING: Prospective cohort study testing the Confusion Assessment Method for ICU Patients (CAM-ICU) in the adult medical and coronary ICUs of a US university-based medical center. PARTICIPANTS: A total of 111 consecutive patients who were mechanically ventilated were enrolled from February 1, 2000, to July 15, 2000, of whom 96 (86.5%) were evaluable for the development of delirium and 15 (13.5%) were excluded because they remained comatose throughout the investigation. MAIN OUTCOME MEASURES: Occurrence rate of delirium and sensitivity, specificity, and interrater reliability of delirium assessments using the CAM-ICU, made daily by 2 critical care study nurses, compared with assessments by delirium experts using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. RESULTS: A total of 471 daily paired evaluations were completed. Compared with the reference standard for diagnosing delirium, 2 study nurses using the CAM-ICU had sensitivities of 100% and 93%, specificities of 98% and 100%, and high interrater reliability (kappa = 0.96; 95% confidence interval, 0.92-0.99). Interrater reliability measures across subgroup comparisons showed kappa values of 0.92 for those aged 65 years or older, 0.99 for those with suspected dementia, or 0.94 for those with Acute Physiology and Chronic Health Evaluation II scores at or above the median value of 23 (all P<.001). Comparing sensitivity and specificity between patient subgroups according to age, suspected dementia, or severity of illness showed no significant differences. The mean (SD) CAM-ICU administration time was 2 (1) minutes. Reference standard diagnoses of delirium, stupor, and coma occurred in 25.2%, 21.3%, and 28.5% of all observations, respectively. Delirium occurred in 80 (83.3%) patients during their ICU stay for a mean (SD) of 2.4 (1.6) days. Delirium was even present in 39.5% of alert or easily aroused patient observations by the reference standard and persisted in 10.4% of patients at hospital discharge. CONCLUSIONS: Delirium, a complication not currently monitored in the ICU setting, is extremely common in mechanically ventilated patients. The CAM-ICU appears to be rapid, valid, and reliable for diagnosing delirium in the ICU setting and may be a useful instrument for both clinical and research purposes.

What does the medical record reveal about functional status? A comparison of medical record and interview data.

OBJECTIVE: Functional status measures are potent independent predictors of hospital outcomes and mortality. The study objective was to compare medical record with interview data for functional status. SUBJECTS AND METHODS: Subjects were 525 medical patients, aged 70 years or older, hospitalized at an academic medical center. Patient interviews determined status for 7 basic activities of daily living (BADLs) and 7 instrumental activities of daily living (IADLs). Medical records were reviewed to assess documentation of BADLs and IADLs. RESULTS: Most medical records contained no documentation of individual BADLs and IADLs (61% to 98% of records lacking documentation), with the exception of walking (24% of medical records lacking documentation). Impairment prevalence was lower in medical records than at interview for all BADLs and IADLs, and agreement between interview and medical record was poor (kappa < 0.40 for individual BADLs and IADLs). Sensitivity of the medical record for BADL and IADL impairment was poor (range 95% to 44%), using the interview as a reference standard. Sensitivity and specificity of the medical record for detection of BADL and IADL impairment changed substantially when records with nondocumentation of functional status were excluded or were assumed to be equivalent to independence. CONCLUSIONS: The results suggest that the medical record is a poor source of data on many functional status measures, and that assuming that nondocumentation of functional status is equivalent to independence may be unwarranted. Given the prognostic importance of functional status measures, the results highlight the importance of developing reliable and efficient means of obtaining functional status information on hospitalized older patients.

An algorithm for prospective individual matching in a non-randomized clinical trial.

A method is described to achieve balance across prognostic factors in intervention trials for which randomized allocation to treatment group is not possible. The method involves prospective individual matching of patients that have already been assigned to treatment groups. Data can be analyzed using methods appropriate for prospective matched cohort studies. Successful implementation depends on the number and complexity of factors to be matched, and on the number of available control patients. Simulation studies suggest that, in order to yield satisfactory match rates and to reduce costs associated with screening unmatched controls, no more than three prognostic factors should generally be considered. Baseline prognostic indices, incorporating information from multiple variables, provide effective matching factors. The implementation of the method in a successful clinical trial, the Delirium Prevention Trial, is discussed. In that study, treatment group was determined by hospital admission to either an intervention floor or to one of two usual care hospital floors. The ratio of available control to intervention patients was 1.3, and 95% of the eligible intervention floor patients were successfully matched to control floor patients. Excellent balance was demonstrated for non-matching factors, due in part to the use of a composite baseline risk score as a matching factor. In addition, external validity is enhanced because most eligible intervention patients are enrolled as they present. The methods outlined in this report provide a methodologically rigorous alternative for achieving balance across treatment groups, with respect to important prognostic factors, in non-randomized clinical trials, and will have broad applicability in the numerous situations in which randomization is not possible.

Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients.

BACKGROUND: Diphenhydramine hydrochloride is a commonly prescribed medicine in hospitalized patients, but its adverse effects on older patients remain unclear. METHODS: We enrolled 426 hospitalized medical patients aged 70 years or older in a prospective cohort study in a university hospital. Measurements included baseline and daily assessments including Mini-Mental State Examination scores, Confusion Assessment Method ratings, direct observations for medical devices (urinary catheter or physical restraints), and blinded medical record extractions for diphenhydramine use. RESULTS: Of the 426 patients, 114 (27%) received diphenhydramine during hospitalization and shared similar baseline characteristics including age, sex, delirium risk, and Mini-Mental State Examination scores compared with nonexposed patients. The diphenhydramine-exposed group was at an increased risk for any delirium symptoms (relative risk [RR], 1.7; 95% confidence interval [CI], 1.3-2.3) and for individual delirium symptoms, including inattention (RR, 3.0; 95% CI, 1.5-5.9), disorganized speech (RR, 5.5; 95% CI, 1.0-29.8), and altered consciousness (RR, 3.1; 95% CI, 1.6-6.1). Exposed patients also had increased risk for urinary catheter placement (RR, 2.5; 95% CI, 1.0-6.0) and longer median length of stay (7 vs 6 days; P =.009). A dose-response relationship was demonstrated for most adverse outcomes. Overall, 24% of diphenhydramine doses were administered inappropriately. CONCLUSIONS: Diphenhydramine administration in older hospitalized patients is associated with an increased risk of cognitive decline and other adverse effects with a dose-response relationship. Careful review of its use is necessary in this vulnerable population.

Diagnosis and management of delirium near the end of life.

Delirium is a common and distressing symptom that constitutes a significant challenge for end-of-life care. However, reliable techniques are available for the diagnosis of delirium, and effective therapies exist as well. This consensus paper uses a case-based format that begins with an overview of the definition and presentation of delirium. Next, strategies for diagnosis are suggested, with attention to the unique challenges that clinicians face in pursuing a diagnostic work-up for patients near the end of life. The paper concludes with a review of therapeutic options.

Risk adjustment for older hospitalized persons: a comparison of two methods of data collection for the Charlson index.

To compare Charlson indices based on chart data and ICD-9 data for agreement overall and on rating specific comorbid conditions, and to compare mortality risks associated with these indices. Prospective cohort study. Six general medicine wards at Yale-New Haven Hospital. 524 consecutive patients who had no clinical evidence of delirium at enrollment, admitted between November 6, 1989 and July 31, 1991, aged 70 years or older. Death within 1 year of the index hospital admission date. Scores using the chart-based data were significantly higher than those using ICD-9 data. About half of the individual conditions showed fair-to-good agreement between the two scores, whereas the other half showed poor agreement. A comparison of mortality prediction indicated that the weightings assigned to individual comorbidities differed substantially from those used in Charlson's original index. While mortality prediction of each individual index was comparable, the ICD-9 and chart indices contributed independently to mortality prediction in the presence of the other. Low agreement between Charlson scores based on the two methods of data collection and their cumulative contribution to mortality prediction suggest that these indices may include different information. Our results suggest that the original Charlson index may not provide optimal risk adjustment for elderly general medicine samples. We suggest development of an empirically-derived index of comorbid conditions and weights may be warranted for older general medical patients.

Multicomponent targeted intervention to prevent delirium in hospitalized older patients: what is the economic value?

INTRODUCTION: Delirium, or acute confusional state, is a common and serious occurrence among hospitalized older persons. Current estimates suggest that delirium complicates hospital stays for more than 2.3 million older persons each year, involving more than 17.5 million hospital days and accounting for more than $4 billion (1994 dollars) of Medicare expenditures. A 40% reduction was recently reported in the risk for delirium among hospitalized older persons receiving a multicomponent targeted risk factor intervention (MTI) strategy to prevent delirium, compared with subjects receiving usual hospital care.1 Before recommending that this preventive strategy be implemented in clinical practice, however, the cost implications must be thoroughly examined as well. METHODS: The present analysis performs net cost evaluations of the MTI for the prevention of delirium among hospitalized patients. Hospital charge and cost-to-charge ratio data are linked to a database of 852 subjects, who were treated with MTI or usual care. Multivariable regression methods were used to help isolate the impact of MTI on hospital costs. These results were then combined with our earlier work on the impact of the MTI on delirium prevention to assess the cost effectiveness of this intervention. RESULTS: The MTI significantly reduced nonintervention costs among subjects at intermediate risk for developing delirium, but not among subjects at high risk. When MTI intervention costs were included, MTI had no significant effect on overall health care costs in the intermediate risk cohort, but raised overall costs in the high risk group. CONCLUSIONS: Because the MTI prevented delirium in the intermediate risk group without raising costs, the conclusion reached is that it is a cost effective treatment option for patients at intermediate risk for developing delirium. In contrast, the results suggest that the MTI is not cost effective for subjects at high risk.

Dementia and race: are there differences between African Americans and Caucasians?

This study provides an overview of racial differences in etiology and prevalence of dementia. Preliminary findings indicate that the clinical and molecular etiologies of dementia differ between races. African Americans have a higher prevalence of vascular dementia and a lower prevalence of Parkinsonian dementia than do Caucasians. The genetic etiologies of Alzheimer's-type dementia appear to differ between African Americans and Caucasians. The variations in dementia etiologies and in cognitive testing accuracy between races suggests the urgent need to develop racially appropriate cognitive assessment methods and to develop preventive and treatment etiologies differently according to racial background of individual patients.

Methodologic issues in conducting research on hospitalized older people.

OBJECTIVE: To describe challenges in conducting research with hospitalized geriatric patients. DESIGN: Quasi-experimental longitudinal study with inperson interviews at baseline and discharge and a three-month postdischarge telephone interview. Study protocol required baseline interviews within 48 hours of admission for patients or 72 hours for proxies. SETTING: 813-bed urban teaching hospital. PARTICIPANTS: 240 patients, mean age 83.8 years, at moderate to high risk for functional decline during hospitalization, admitted from the emergency room to a general medical unit. MEASUREMENTS: Delays starting or interruptions continuing interviews; patient and environmental conditions potentially affecting data quality; and information on proxy use. RESULTS: Timely access to patients or proxies was a major difficulty, resulting in the screening of only 53.1% of 867 potentially eligible patients. Multiple patient contacts and visits were required to complete interviews. Only 61.3% of baseline and 28.1% of follow-up interviews were completed on the initial day of contact. Despite having on-site interviewers 7 days a week, 29% of discharge interviews were conducted by telephone. Interviews were >90% complete in 487 of 503 of encounters (97%). Baseline delays and interruptions were usually due to the presence of medical staff, off-unit tests, patient illness, nurse unavailability for interview, and need for a proxy. Most in-hospital interviews were conducted with others present. Proxies were required for approximately one-third of patients at all three interviews. CONCLUSION: Conducting clinical research with older adults in the current inpatient setting, where patients are more severely ill yet have shorter lengths of stay now than in the past, proves a challenging yet achievable goal. Effective procedures for negotiating the acute care environment are critical to successful studies.

Goals for the care of frail older adults: do caregivers and clinicians agree?

PURPOSE: Establishing shared treatment goals for patients may improve the quality of care by facilitating achievement of appropriate and desired outcomes. The purpose of this study was to describe types of family caregiver and physician treatment goals for frail elderly patients who had a high prevalence of cognitive impairment, and to ascertain the level of agreement between family caregivers and physicians on principal treatment goals. SUBJECTS AND METHODS: We surveyed family caregivers and physicians for 200 consecutive older adults who were initially evaluated at the outpatient geriatric assessment center of a major teaching hospital. Treatment goals for patients were measured after a comprehensive geriatric assessment. RESULTS: Goals commonly chosen as most important by family caregivers and physicians pertained to day-to-day functioning (61 [31%] family caregivers, 81 [41%] physicians), behavior and emotional health (56 [28%] family caregivers, 50 [25%] physicians), and safety (40 [20%] family caregivers, 29 [15%] physicians). Although a substantial proportion of family caregiver and physician pairs shared at least one goal (157 [79%] of 200), agreement on presence or absence of individual categories of goals was poor (kappas from -0.19 to 0.28), and agreement on the most important goal was also poor (kappa 0.20). CONCLUSIONS: Agreement on treatment goals between family caregivers and physicians for patients at the study site was low. These results suggest that encounters between family caregiver and physician may need improvement. Further research is needed to assess whether lack of agreement is found in other settings, persists over time, and affects achievement of goals and optimal health outcomes.

The impact of delirium in the intensive care unit on hospital length of stay.

STUDY OBJECTIVE: To determine the relationship between delirium in the intensive care unit (ICU) and outcomes including length of stay in the hospital. DESIGN: A prospective cohort study. SETTING: The adult medical ICU of a tertiary care, university-based medical center. PARTICIPANTS: The study population consisted of 48 patients admitted to the ICU, 24 of whom received mechanical ventilation. MEASUREMENTS: All patients were evaluated for the development and persistence of delirium on a daily basis by a geriatric or psychiatric specialist with expertise in delirium assessment using the Diagnostic Statistical Manual IV (DSM-IV) criteria of the American Psychiatric Association, the reference standard for delirium ratings. Primary outcomes measured were length of stay in the ICU and hospital. RESULTS: The mean onset of delirium was 2.6 days (S.D.+/-1.7), and the mean duration was 3.4+/-1.9 days. Of the 48 patients, 39 (81.3%) developed delirium, and of these 29 (60.4%) developed the complication while still in the ICU. The duration of delirium was associated with length of stay in the ICU ( r=0.65, P=0.0001) and in the hospital ( r=0.68, P<0.0001). Using multivariate analysis, delirium was the strongest predictor of length of stay in the hospital ( P=0.006) even after adjusting for severity of illness, age, gender, race, and days of benzodiazepine and narcotic drug administration. CONCLUSIONS: In this patient cohort, the majority of patients developed delirium in the ICU, and delirium was the strongest independent determinant of length of stay in the hospital. Further study and monitoring of delirium in the ICU and the risk factors for its development are warranted.

Delirium in the intensive care unit: an under-recognized syndrome of organ dysfunction.

The intensivist should think of delirium, or acute central nervous system dysfunction, as the brain's form of "organ dysfunction.'' Delirium is extremely common in intensive care unit (ICU) patients due to factors such as comorbidity, critical illness, and iatrogenesis. This complication of hospital stay is extremely hazardous in older persons and is associated with prolonged hospital stays, institutionalization, and death. Neurologic dysfunction compromises patients' ability to be removed from mechanical ventilation or achieve full recovery and independence. Yet ICU nurses and physicians are usually unaware of the presence of hypoactive delirium and only recognize this disturbance in agitated patients (hyperactive delirium). More importantly, there are few studies that have included ICU patients in the assessment or prevention of delirium. This article reviews the definition and salient features of delirium, its primary risk factors, a newly validated instrument for delirium assessment that is being developed for ICU nurses and physicians, and pharmacological agents associated with the development of delirium and used in its management.

The Hospital Elder Life Program: a model of care to prevent cognitive and functional decline in older hospitalized patients. Hospital Elder Life Program.

OBJECTIVES: To describe the Hospital Elder Life Program, a new model of care designed to prevent functional and cognitive decline of older persons during hospitalization. PROGRAM STRUCTURE AND PROCESS: All patients aged > or =70 years on specified units are screened on admission for six risk factors (cognitive impairment, sleep deprivation, immobility, dehydration, vision or hearing impairment). Targeted interventions for these risk factors are implemented by an interdisciplinary team-including a geriatric nurse specialist, Elder Life Specialists, trained volunteers, and geriatricians--who work closely with primary nurses. Other experts provide consultation at twice-weekly interdisciplinary rounds. INTERVENTION: Adherence is carefully tracked. Quality assurance procedures and performance reviews are an integral part of the program. PROGRAM OUTCOMES: To date, 1,507 patients have been enrolled during 1,716 hospital admissions. The overall intervention adherence rate was 89% for at least partial adherence with all interventions during 37,131 patient-days. Our results indicate that only 8% of admissions involved patients who declined by 2 or more points on MMSE and only 14% involved patients who declined by 2 or more points on ADL score. Comparative results for the control group from the clinical trial were 26% and 33%, and from previous studies 14 to 56% and 34 to 50% for cognitive and functional decline, respectively. Effectiveness of the program for delirium prevention and of the program's nonpharmacologic sleep protocol have been demonstrated previously. CONCLUSIONS: These results suggest that the Hospital Elder Life Program successfully prevents cognitive and functional decline in at-risk older patients. The program is unique in its hospital-wide focus; in providing skilled staff and volunteers to implement interventions; and in targeting practical interventions toward evidence-based risk factors. Future studies are needed to evaluate cost-effectiveness and longterm outcomes of the program as well as its effectiveness in non-hospital settings.

Prevention of delirium in hospitalized older patients: risk factors and targeted intervention strategies.

Delirium is a common, costly, and potentially devastating condition for hospitalized older patients. Delirium is a multifactorial syndrome, involving the inter-relationship between patient vulnerability, or predisposing factors at admission, and noxious insults or precipitating factors during hospitalization. Through a series of studies, we first identified significant predisposing factors for delirium, including vision impairment, severe illness, cognitive impairment, and dehydration. Subsequently, significant precipitating factors were identified, including physical restraint use, malnutrition, adding more than three drugs, bladder catheter use, and any iatrogenic event. Through targeting preventive strategies towards six identified risk factors in a controlled clinical trial, we were successful in the primary prevention of delirium. In 852 subjects, the incidence of delirium was significantly reduced in the intervention group compared with usual care (9.9% vs 15.0%, matched odds ratio: 0.60; 95% confidence interval: 0.39-0.92). The total number of days and episodes of delirium were also significantly reduced in the intervention group. Based on this work, evidence-based recommendations for delirium prevention are proposed. While not all cases of delirium will be preventable with this approach, unifying medical and epidemiological approaches to delirium represents a key advance essential to reducing the high morbidity and mortality associated with delirium in the older population.