Publications

OBJECTIVES: To compare chart- and interview-based methods for identification of delirium.

DESIGN: Prospective cohort study.

SETTING: Two academic medical centers.

PARTICIPANTS: Individuals aged 70 and older undergoing major elective surgery (N = 300) (majority orthopedic surgery).

MEASUREMENTS: Participants were interviewed daily during hospitalization for delirium using the Confusion Assessment Method (CAM; interview-based method), and their medical charts were reviewed for delirium using a validated chart-review method (chart-based method). Rate of agreement of the two methods and characteristics of those identified using each approach were examined. Predictive validity for clinical outcomes (length of stay, postoperative complications, discharge disposition) was compared. In the absence of a criterion standard, predictive value could not be calculated.

RESULTS: The cumulative incidence of delirium was 23% (n = 68) according to the interview-based method, 12% (n = 35) according to the chart-based method, and 27% (n = 82) according to the combined approach. Overall agreement was 80%; kappa was 0.30. The methods differed in detection of psychomotor features and time of onset. The chart-based method missed delirium in individuals that the CAM identified who were lacking features of psychomotor agitation or inappropriate behavior. The CAM-based method missed chart-identified cases occurring during the night shift. The combined method had high predictive validity for all clinical outcomes.

CONCLUSIONS: Interview- and chart-based methods have specific strengths for identification of delirium. A combined approach captures the largest number and broadest range of delirium cases.

BACKGROUND: Quantifying the severity of delirium is essential to advancing clinical care by improved understanding of delirium effect, prognosis, pathophysiology, and response to treatment.

OBJECTIVE: To develop and validate a new delirium severity measure (CAM-S) based on the Confusion Assessment Method.

DESIGN: Validation analysis in 2 independent cohorts.

SETTING: Three academic medical centers.

PATIENTS: The first cohort included 300 patients aged 70 years or older scheduled for major surgery. The second included 919 medical patients aged 70 years or older.

MEASUREMENTS: A 4-item short form and a 10-item long form were developed. Association of the maximum CAM-S score during hospitalization with hospital and posthospital outcomes related to delirium was evaluated.

RESULTS: Representative results included adjusted mean length of stay, which increased across levels of short-form severity from 6.5 days (95% CI, 6.2 to 6.9 days) to 12.7 days (CI, 11.2 to 14.3 days) (P for trend < 0.001) and across levels of long-form severity from 5.6 days (CI, 5.1 to 6.1 days) to 11.9 days (CI, 10.8 to 12.9 days) (P for trend < 0.001). Representative results for the composite outcome of adjusted relative risk of death or nursing home residence at 90 days increased progressively across levels of short-form severity from 1.0 (referent) to 2.5 (CI, 1.9 to 3.3) (P for trend < 0.001) and across levels of long-form severity from 1.0 (referent) to 2.5 (CI, 1.6 to 3.7) (P for trend < 0.001).

LIMITATION: Data on clinical outcomes were measured in an older data set limited to patients aged 70 years or older.

CONCLUSION: The CAM-S provides a new delirium severity measure with strong psychometric properties and strong associations with important clinical outcomes.

PRIMARY FUNDING SOURCE: National Institute on Aging.

OBJECTIVES: To create a risk prediction rule for delirium in elderly adults in the emergency department (ED) and to compare mortality and resource use of elderly adults in the ED with and without delirium.

DESIGN: Prospective observational study.

SETTING: Urban tertiary care ED.

PARTICIPANTS: Individuals aged 65 and older presenting for ED care (N = 700).

MEASUREMENTS: A trained research assistant performed a structured mental status assessment and attention tests, after which delirium was determined using the Confusion Assessment Method. Data were collected on participant demographics, comorbidities, medications, ED course, hospital and intensive care unit (ICU) admission, length of stay, hospital charges, 30-day rehospitalization, and mortality.

RESULTS: Nine percent of elderly study participants had delirium. Using logistic regression, a delirium prediction rule consisting of older age, prior stroke or transient ischemic attack, dementia, suspected infection, and acute intracranial hemorrhage was created had good predictive accuracy (area under the receiver operating characteristic curve = 0.77). Admitted participants with ED delirium had longer median lengths of stay (4 vs 2 days) and were more likely to require ICU admission (13% vs 6%) and to be discharged to a new long-term care facility (37% vs 9%) than those without. In all participants, ED delirium was associated with higher 30-day mortality (6% vs 1%) and 30-day readmission (27% vs 13%).

CONCLUSION: This risk prediction rule may help identify a group of individuals in the ED at high risk of developing delirium who should undergo screening, but it requires external validation. Identification of delirium in the ED may enable physicians to implement strategies to decrease delirium duration and avoid inappropriate discharge of individuals with acute delirium, improving outcomes.

Post-operative cognitive dysfunction is associated with morbidity and mortality. However, its neuropathogenesis remains largely to be determined. Neuroinflammation and accumulation of β-amyloid (Aβ) have been reported to contribute to cognitive dysfunction in humans and cognitive impairment in animals. Our recent studies have established a pre-clinical model in mice, and have found that the peripheral surgical wounding without the influence of general anesthesia induces an age-dependent Aβ accumulation and cognitive impairment in mice. We therefore set out to assess the effects of peripheral surgical wounding, in the absence of general anesthesia, on neuroinflammation in mice with different ages. Abdominal surgery under local anesthesia was established in 9 and 18 month-old mice. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Iba1 positive cells (the marker of microglia activation), CD33, and cognitive function in mice were determined. The peripheral surgical wounding increased the levels of TNF-α, IL-6, and Iba1 positive cells in the hippocampus of both 9 and 18 month-old mice, and age potentiated these effects. The peripheral surgical wounding increased the levels of CD33 in the hippocampus of 18, but not 9, month-old mice. Finally, anti-inflammatory drug ibuprofen ameliorated the peripheral surgical wounding-induced cognitive impairment in 18 month-old mice. These data suggested that the peripheral surgical wounding could induce an age-dependent neuroinflammation and elevation of CD33 levels in the hippocampus of mice, which could lead to cognitive impairment in aged mice. Pending further studies, anti-inflammatory therapies may reduce the risk of postoperative cognitive dysfunction in elderly patients.

OBJECTIVES: To determine whether a bundled intervention can increase detection of delirium and facilitate safer use of high-risk medications.

DESIGN: Pre-post interventional trial.

SETTING: Large academic medical center.

PARTICIPANTS: Individuals aged 70 and older (n = 19,949) admitted between May 1, 2008, September 30, 2011. Individuals aged 80 and older admitted after April 26, 2010, received the intervention, those aged 80 and older admitted before were primary controls, and those aged 70 to 79 were concurrent controls.

INTERVENTION: The intervention uses a checklist promoting delirium prevention, recognition and management, and modifies the computerized provider order entry system to provide care focused on elderly adults.

MEASUREMENTS: Frequency of orders for activating the rapid response team for altered mental status, frequency of orders for haloperidol in excess of 0.5 mg or intravenous (IV) morphine in excess of 2 mg, and discharge disposition.

RESULTS: Participants receiving the intervention had a mean age of 86.1 ± 4.6; 58.2% were female. The number of orders to activate the rapid response team for altered mental status increased in participants receiving the bundle and in controls (odds ratio (OR) for the difference of differences = 1.23 (95% confidence interval (CI) = 0.68-2.24, P = .49)). Participants receiving the bundle were less likely to receive more than 0.5 mg of IV, intramuscular, or oral haloperidol (OR = 0.60, 95% CI = 0.39-0.91, P = .02) and more than 2 mg of IV morphine (OR = 0.52, 95% CI = 0.42-0.63, P < .001). Participants who received the bundle were more likely to be discharged home than to extended care facilities (OR = 1.18, 95% CI = 1.04-1.35, P = .01).

CONCLUSION: An intervention focused on delirium prevention and recognition by bedside staff combined with computerized decision support facilitates safer prescribing of high-risk medications and possibly results in less need for extended care.

OBJECTIVE: The neuropathogenesis of postoperative delirium remains unknown. Low cerebrospinal fluid (CSF) βamyloid protein (Aβ) and high CSF Tau levels are associated with Alzheimer's disease. We therefore assessed whether lower preoperative CSF Aβ/Tau ratio was associated with higher incidence and greater severity of postoperative delirium.

METHODS: One hundred and fifty three participants (71±5 years, 53% males) who had total hip/knee replacement under spinal anesthesia were enrolled. CSF was obtained during initiation of spinal anesthesia. The incidence and severity of postoperative delirium were determined by Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS) on postoperative day 1 and 2. Aβ40, Aβ42, and Tau levels in the CSF were measured by enzyme-linked immunosorbent assay. The relationships among these variables were determined, adjusting for age and gender.

RESULTS: Participants in the lowest quartile of preoperative CSF Aβ40/Tau and Aβ42/Tau ratio had higher incidence (32% versus 17%, P=0. 0482) and greater symptom severity of postoperative delirium (Aβ40/Tau ratio: 4 versus 3, P=0. 034; Aβ42/Tau ratio: 4 versus 3, P=0. 062, the median of the highest Memorial Delirium Assessment Scale score) as compared to the combination of the rest of the quartiles. The preoperative CSF Aβ40/Tau or Aβ42/Tau ratio was inversely associated with Memorial Delirium Assessment Scale score (Aβ40/Tau ratio: -0.12±0.05, P=0.014, adj. -0.12±0.05, P=0.018; Aβ42/Tau ratio: -0.65±0.26, P=0.013, adj. -0.62±0.27, P=0.022).

INTERPRETATION: Lower CSF Aβ/Tau ratio could be associated with postoperative delirium, pending confirmation of our preliminary results in further studies. These findings suggest potential roles of Aβ and/or Tau in postoperative delirium neuropathogenesis.

Delirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent memory. However, clinical manifestations and imaging studies point to abnormalities not in the hippocampus but in cortical circuits. We therefore tested the hypothesis that systemic inflammation impairs prefrontal cortex function by assessing attention and executive function in aged animals. Aged (24-month-old) Fischer-344 rats received a single intraperitoneal injection of lipopolysaccharide (LPS; 50 μg/kg) or saline and were tested on the attentional set-shifting task (AST), an index of integrity of the prefrontal cortex, on days 1-3 post-injection. Plasma and frontal cortex concentrations of the cytokine TNFα and the chemokine CCL2 were measured by ELISA in separate groups of identically treated, age-matched rats. LPS selectively impaired reversal learning and attentional shifts without affecting discrimination learning in the AST, indicating a deficit in attention and cognitive flexibility but not learning globally. LPS increased plasma TNFα and CCL2 acutely but this resolved within 24-48 h. TNFα in the frontal cortex did not change whereas CCL2 increased nearly threefold 2 h after LPS but normalized by the time behavioral testing started 24 h later. Together, our data indicate that systemic inflammation selectively impairs attention and executive function in aged rodents and that the cognitive deficit is independent of concurrent changes in frontal cortical TNFα and CCL2. Because inattention is a prominent feature of clinical delirium, our data support a role for inflammation in the pathogenesis of this clinical syndrome and suggest this animal model could be useful for studying that relationship further.

BACKGROUND: Little is known about older women's experience with a benign breast biopsy.

OBJECTIVES: To examine the psychological impact and experience of women ≥ 65 years of age with a benign breast biopsy.

DESIGN: Prospective cohort study using quantitative and qualitative methods.

SETTING: Three Boston-based breast imaging centers.

PARTICIPANTS: Ninety-four English-speaking women ≥ 65 years without dementia referred for breast biopsy as a result of an abnormal mammogram, not aware of their biopsy results at baseline, and with a subsequent negative biopsy.

MEASUREMENTS: We interviewed women at the time of breast biopsy (before women knew their results) and 6 months post-biopsy. At both interviews, participants completed the validated negative psychological consequences of screening mammography questionnaire (PCQ, scores range from 0 to 36 [high distress], PCQ ≥ 1 suggests a psychological consequence, PCQs <1 are reported at time of screening) and women responded to open-ended questions about their experience. At follow-up, participants described the quality of information received after their benign breast biopsy. We used a linear mixed effects model to examine if PCQs declined over time. We also reviewed participants' open-ended comments for themes.

RESULTS: Overall, 88% (83/94) of participants were non-Hispanic white and 33% (31/94) had a high-school degree or less. At biopsy, 76% (71/94) reported negative psychological consequences from their biopsy compared to 39% (37/94) at follow-up (p < 0.01). In open-ended comments, participants noted the anxiety (29%, 27/94) and discomfort (28%, 26/94) experienced at biopsy (especially from positioning on the biopsy table). Participants requested more information to prepare for a biopsy and to interpret their negative results. Forty-four percent (39/89) reported at least a little anxiety about future mammograms.

CONCLUSIONS: The high psychological burden of a benign breast biopsy among older women significantly diminishes with time but does not completely resolve. To reduce this burden, older women need more information about undergoing a breast biopsy.

BACKGROUND: Delirium is common, leads to other adverse outcomes, and is costly. However, it often remains unrecognized in most clinical settings. The Confusion Assessment Method (CAM) is the most widely used diagnostic algorithm, and operationalizing its features would be a substantial advance for clinical care.

OBJECTIVE: To derive the 3D-CAM, a new 3-minute diagnostic assessment for CAM-defined delirium, and validate it against a clinical reference standard.

DESIGN: Derivation and validation study.

SETTING: 4 general medicine units in an academic medical center.

PARTICIPANTS: 201 inpatients aged 75 years or older.

MEASUREMENTS: 20 items that best operationalized the 4 CAM diagnostic features were identified to create the 3D-CAM. For prospective validation, 3D-CAM assessments were administered by trained research assistants. Clinicians independently did an extensive assessment, including patient and family interviews and medical record reviews. These data were considered by an expert panel to determine the presence or absence of delirium and dementia (reference standard). The 3D-CAM delirium diagnosis was compared with the reference standard in all patients and subgroups with and without dementia.

RESULTS: The 201 participants in the prospective validation study had a mean age of 84 years, and 28% had dementia. The expert panel identified 21% with delirium, 88% of whom had hypoactive or normal psychomotor features. Median administration time for the 3D-CAM was 3 minutes (interquartile range, 2 to 5 minutes), sensitivity was 95% (95% CI, 84% to 99%), and specificity was 94% (CI, 90% to 97%). The 3D-CAM did well in patients with dementia (sensitivity, 96% [CI, 82% to 100%]; specificity, 86% [CI, 67% to 96%]) and without dementia (sensitivity, 93% [CI, 66% to 100%]; specificity, 96% [CI, 91% to 99%]).

LIMITATION: Limited to single-center, cross-sectional, and medical patients only.

CONCLUSION: The 3D-CAM operationalizes the CAM algorithm using a 3-minute structured assessment with high sensitivity and specificity relative to a reference standard and could be an important tool for improving recognition of delirium.

PRIMARY FUNDING SOURCE: National Institute on Aging.