Publications

CONTEXT: Older adults with end-stage renal disease (ESRD) are a rapidly growing group of seriously ill patients. Yet, despite a mortality rate almost twice that of cancer, less is known about the impact of ESRD on patients' end-of-life experience.

OBJECTIVE: To compare the end-of-life experience of older adults who died of ESRD vs. cancer.

METHODS: We used data from the Health and Retirement Study, a nationally representative survey of older adults. Our sample included 1883 Health and Retirement Study participants who died of cancer or ESRD between 2000 and 2010 and their family respondents. We compared advance care planning, treatment intensity, and symptoms between the two groups and used propensity score weighting to adjust for differences by diagnosis.

RESULTS: Among propensity-weighted cohorts, older adults with ESRD, compared with similar patients with cancer, were less likely to have end-of-life instructions (adjusted proportions 38.5% vs. 49.7%; P = 0.005) and were more likely to die in the hospital (53.5% vs. 29.0%; P < 0.001) and to use the intensive care unit in the last two years of life (57.1% vs. 37.0%; P < 0.001). Decedents with ESRD and cancer had similarly high rates of moderate or severe pain (53.7% vs. 57.8%; P = 0.34) and all other symptoms.

CONCLUSION: Older adults dying of ESRD had lower rates of advance care planning and higher treatment intensity near the end of life than similar patients dying of cancer; both groups had similarly high rates of symptoms. Efforts are needed to make treatment more supportive and alleviate suffering for older adults with ESRD and their families near the end of life.

OBJECTIVE: To investigate the effect of postoperative delirium on longitudinal brain microstructural changes, as measured by diffusion tensor imaging.

METHODS: We studied a subset of the larger Successful Aging after Elective Surgery (SAGES) study cohort of older adults (≥70 years) without dementia undergoing elective surgery: 113 participants who had diffusion tensor imaging before and 1 year after surgery. Postoperative delirium severity and occurrence were assessed during the hospital stay using the Confusion Assessment Method and a validated chart review method. We investigated the association of delirium severity and occurrence with longitudinal diffusion changes across 1 year, adjusting for age, sex, vascular comorbidity, and baseline cognitive performance. We also assessed the association between changes in diffusion and cognitive performance across the 1-year follow-up period, adjusting for age, sex, education, and baseline cognitive performance.

RESULTS: Postoperative delirium occurred in 25 participants (22%). Delirium severity and occurrence were associated with longitudinal diffusion changes in the periventricular, frontal, and temporal white matter. Diffusion changes were also associated with changes in cognitive performance across 1 year, although the cognitive changes did not show significant association with delirium severity or occurrence.

CONCLUSIONS: Our study raises the possibility that delirium has an effect on the development of brain microstructural abnormalities, which may reflect brain changes underlying cognitive trajectories. Future studies are warranted to clarify whether delirium is the driving factor of the observed changes or rather a correlate of a vulnerable brain that is at high risk for neurodegenerative processes.

Patients with dementia due to Alzheimer's disease (AD) have increased risk of developing delirium. This study investigated the relationship between a magnetic resonance imaging (MRI)-derived biomarker associated with preclinical AD and postoperative delirium. Participants were older adults (≥70 years) without dementia who underwent preoperative MRI and elective surgery. Delirium incidence and severity were evaluated daily during hospitalization. Cortical thickness was averaged across a published set of a priori brain regions to derive a measure known as the "AD signature." Logistic and linear regression was used, respectively, to test whether the AD signature was associated with delirium incidence in the entire sample (N = 145) or with the severity of delirium among those who developed delirium (N = 32). Thinner cortex in the AD signature did not predict incidence of delirium (odds ratio = 1.15, p = 0.38) but was associated with greater delirium severity among those who developed delirium (b = -1.2, p = 0.014). These results suggest that thinner cortices, perhaps reflecting underlying neurodegeneration due to preclinical AD, may serve as a vulnerability factor that increases severity once delirium occurs.

OBJECTIVES: To survey the current methods used to ascertain dementia and mild cognitive impairment (MCI) in longitudinal cohort studies, to categorize differences in approaches and to identify key components of expert panel methodology in current use.

METHODS: We searched PubMed for the past 10 years, from March 6, 2007 to March 6, 2017 using a combination of controlled vocabulary and keyword terms to identify expert panel consensus methods used to diagnose MCI or dementia in large cohort studies written in English. From these results, we identified a framework for reporting standards and describe as an exemplar the clinical consensus procedure used in an ongoing study of elective surgery patients (the Successful Aging after Elective Surgery study).

RESULTS: Thirty-one articles representing unique cohorts were included. Among published methods, membership of experts panel varied significantly. There was more similarity in what types of information was use to ascertain disease status. However, information describing the diagnostic decision process and resolution of disagreements was often lacking.

CONCLUSIONS: Methods used for expert panel diagnosis of MCI and dementia in large cohort studies are widely variable, and there is a need for more standardized reporting of these approaches. By describing the procedure in which our expert panel achieved consensus diagnoses, we hope to encourage the development and publication of well-founded and reproducible methods for diagnosis of MCI and dementia in longitudinal studies.

A 75-year-old man is admitted for scheduled major abdominal surgery. He is functionally independent, with mild forgetfulness. His intraoperative course is uneventful, but on postoperative day 2, severe confusion and agitation develop. What is going on? How would you manage this patient’s care? Could his condition have been prevented?

We evaluated the role of cognitive and brain reserve markers in modifying the risk of postoperative delirium associated with a pathophysiologic marker. The Successful Aging after Elective Surgery study (SAGES) enrolled 556 adults age ≥70 years without dementia scheduled for major surgery. Patients were assessed preoperatively and daily during hospitalization for delirium. We used C-reactive protein (CRP) as a pathophysiologic marker of inflammation, previously associated with delirium. Markers of reserve included vocabulary knowledge, education, cognitive activities, occupation type and complexity, head circumference, intracranial volume, and leisure activities. Vocabulary knowledge, cognitive activities, and education significantly modified the association of CRP and postoperative delirium ( P < .01). However, effect sizes-when statistically significant-were small in magnitude. The strongest effect modification was observed for vocabulary knowledge: high scores were generally protective but not at high levels of CRP. Select reserve markers attenuate the risk of delirium associated with lower grade inflammatory processes, supporting the role of reserve in delirium.

BACKGROUND/OBJECTIVES: Off-label use of antipsychotics is common in hospitals, most often for delirium management. Antipsychotics have been associated with aspiration pneumonia in community and nursing home settings, but the association in hospitalized individuals is unexplored. We aimed to investigate the association between antipsychotic exposure and aspiration pneumonia during hospitalization.

DESIGN: Retrospective cohort study.

SETTING: Large academic medical center.

PARTICIPANTS: All adult hospitalizations between January 2007 and July 2013. We excluded outside hospital transfers, hospitalizations shorter than 48 hours, and psychiatric hospitalizations.

MEASUREMENTS: Antipsychotic use defined as any pharmacy charge for an antipsychotic medication. Aspiration pneumonia was defined according to a discharge diagnosis code for aspiration pneumonia not present on admission and validated using chart review. A generalized estimating equation was used to control for 43 potential confounders.

RESULTS: Our cohort included 146,552 hospitalizations (median age 56; 39% male). Antipsychotics were used in 10,377 (7.1%) hospitalizations (80% atypical, 35% typical, 15% both). Aspiration pneumonia occurred in 557 (0.4%) hospitalizations. The incidence of aspiration pneumonia was 0.3% in unexposed individuals and 1.2% in those with antipsychotic exposure (odds ratio (OR) = 3.9, 95% confidence interval (CI) = 3.2-4.8). After adjustment, antipsychotic exposure was significantly associated with aspiration pneumonia (adjusted OR = (aOR) = 1.5, 95% CI = 1.2-1.9). Similar results were demonstrated in a propensity-matched analysis and in an analysis restricted to those with delirium or dementia. The magnitude of the association was similar for typical (aOR = 1.4, 95% CI = 0.94-2.2) and atypical (aOR = 1.5, 95% CI = 1.1-2.0) antipsychotics.

CONCLUSION: Antipsychotics were associated with greater odds of aspiration pneumonia after extensive adjustment for participant characteristics. This risk should be considered when prescribing antipsychotics in the hospital.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication of cardiac surgery. Studies have identified potentially injurious roles for cardiopulmonary bypass (CPB) and subsequent reperfusion injury. Cognitive dysfunction has also been linked to the deleterious effects of hyperoxia following ischemia-reperfusion injuries in several disease states, but there has been surprisingly little study into the role of hyperoxia in reperfusion injury after CPB. The potential for tightly regulated intraoperative normoxia to ameliorate the neurocognitive decline following cardiac surgery has not been investigated in a prospective manner. We hypothesize that the use of a protocolized management strategy aimed towards maintenance of an intraoperative normoxic level of oxygen, as opposed to hyperoxia, will reduce the incidence of POCD in older patients undergoing cardiac surgery.

METHODS/DESIGN: One hundred patients aged 65 years and older undergoing non-emergency coronary artery bypass grafting surgery on cardiopulmonary bypass will be enrolled in this prospective, randomized, controlled trial. Subjects will be randomized to receive a fraction of inspired oxygen of either 35% or 100% while under general anesthesia throughout the intraoperative period. The primary outcome measure will be the incidence of POCD in the acute postoperative phase and up to 6 months. The assessment of neurocognition will be undertaken by trained personnel, blinded to study group, with the telephone Montreal Cognitive Assessment (t-MoCA) tool. Secondary outcome measures will include assessment of delirium using the Confusion Assessment Method (CAM and CAM-ICU), as well as time to extubation, days of mechanical ventilation, length of ICU and hospital stay and mortality at 6 months. With the aim of later identifying mechanistic aspects of the effect of oxygen tension, blood, urine, and atrial tissue specimens will be taken at various time points during the perioperative period and later analyzed.

DISCUSSION: This trial will be one of the first randomized controlled studies to prospectively assess the relationship between intraoperative oxygen levels and postoperative neurocognition in cardiac surgery. It addresses a promising biological avenue of intervention in this vulnerable aging population.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02591589 , registered February 13, 2015.

Background: Delirium is associated with many negative health outcomes. Postoperative sedation and opioid administration may contribute to delirium. We hypothesize that the use of dexmedetomidine and Intravenous acetaminophen (IVA) may lead to reduced opioid consumption and decreased incidence of postoperative delirium. This pilot study aims to assess feasibility of using dexmedetomidine and IVA in cardiac surgical patients, and estimate the effect size for incidence and duration of delirium. Methods: A total of 12 adult patients >60 years of age undergoing cardiac surgery were recruited and randomized into 4 groups: Propofol only (P), Propofol with IVA (P+A), Dexmedetomidine only (D), Dexmedetomidine with IVA (D+A). Preoperative baseline cognition and postoperative delirium was assessed daily until discharge. The feasibility was assessed by the number of patients who completed the study. Results: All patients completed the study successfully. The total incidence of delirium in the study population was 42% (5/12):  67% (2/3) in the group P, and 67% (2/3) in the group D, 33% (1/3) in  D+A group and 0%(0/3)  P+A group. The incidence of delirium was 17% (1/6) in the group receiving IVA compared to 67% (4/6) that did not receive IVA. The mean range of duration of delirium was 0-1 days. One patient expired after surgery, unrelated to the study protocol. One patient in the D group experienced hypotension (systolic blood pressure <90 mm of Hg.) Conclusions: The feasibility of performing a  project is ascertained by the study. Patients receiving IVA had lower incidence of delirium compared to patients not receiving IVA which suggests that IVA may have a role in reducing the incidence of delirium. A prospective randomized, placebo-controlled trial will be the next step in investigating the role of dexmedetomidine and IVA in reducing the incidence of delirium.

BACKGROUND: Delirium is common in older hospitalized patients and is associated with poor outcomes, yet most cases go undetected. The best approach for systematic delirium identification outside the intensive care unit remains unknown.

OBJECTIVE: To conduct a comparative effectiveness study of the Confusion Assessment Method for the ICU (CAM-ICU) and the newly developed 3-minute diagnostic assessment for delirium using the Confusion Assessment Method (3D-CAM) in general medicine inpatients.

DESIGN: Cross-sectional comparative effectiveness study.

SETTING: Two non-intensive care general medicine units at a single academic medical center.

PARTICIPANTS: Hospitalized general medicine patients aged ≥75 years.

MEASUREMENTS: Clinicians performed a reference standard assessment for delirium that included patient interviews, family interviews, and review of the medical record. An expert panel determined the presence or absence of delirium using DSM-IV criteria. Two blinded research assistants administered the CAM-ICU and the 3D-CAM in random order, and we determined their diagnostic test characteristics compared to the reference standard.

RESULTS: Among the 101 participants (mean age 84 ± 5.5 years, 61 % women, 25 % with dementia), 19 % were classified as delirious based on the reference standard. Evaluation times for the 3D-CAM and CAM-ICU were similar. The sensitivity [95 % confidence interval (CI)] of delirium detection for the 3D-CAM was 95 % [74 %, 100 %] and for the CAM-ICU was 53 % [29 %, 76 %], while specificity was >90 % for both instruments. Subgroup analyses showed that the CAM-ICU had sensitivity of 30 % in patients with mild delirium vs. 100 % for the 3D-CAM.

CONCLUSIONS: In this comparative effectiveness study, we found that the 3D-CAM had substantially higher sensitivity than the CAM-ICU in hospitalized older general medicine patients, and similar administration time. Therefore, the 3D-CAM may be a superior screening tool for delirium in this patient population.