Publications

BACKGROUND: Systematic screening improves delirium identification among hospitalized older adults. Little data exist on how to implement such screening.

OBJECTIVE: To test implementation of a brief app-directed protocol for delirium identification by physicians, nurses, and certified nursing assistants (CNAs) in real-world practice relative to a research reference standard delirium assessment (RSDA).

DESIGN: Prospective cohort study.

SETTING: Large urban academic medical center and small rural community hospital.

PARTICIPANTS: 527 general medicine inpatients (mean age, 80 years; 35% with preexisting dementia) and 399 clinicians (53 hospitalists, 236 nurses, and 110 CNAs).

MEASUREMENTS: On 2 study days, enrolled patients had an RSDA. Subsequently, CNAs performed an ultra-brief 2-item screen (UB-2) for delirium, whereas physicians and nurses performed a 2-step protocol consisting of the UB-2 followed in those with a positive screen result by the 3-Minute Diagnostic Assessment for the Confusion Assessment Method.

RESULTS: Delirium was diagnosed in 154 of 924 RSDAs (17%) and in 114 of 527 patients (22%). The completion rate for clinician protocols exceeded 97%. The CNAs administered the UB-2 in a mean of 62 seconds (SD, 51). The 2-step protocols were administered in means of 104 seconds (SD, 99) by nurses and 106 seconds (SD, 105) by physicians. The UB-2 had sensitivities of 88% (95% CI, 72% to 96%), 87% (CI, 73% to 95%), and 82% (CI, 65% to 91%) when administered by CNAs, nurses, and physicians, respectively, with specificities of 64% to 70%. The 2-step protocol had overall accuracy of 89% (CI, 83% to 93%) and 87% (CI, 81% to 91%), with sensitivities of 65% (CI, 48% to 79%) and 63% (CI, 46% to 77%) and specificities of 93% (CI, 88% to 96%) and 91% (CI, 86% to 95%), for nurses and physicians, respectively. Two-step protocol sensitivity for moderate to severe delirium was 78% (CI, 54% to 91%).

LIMITATION: Two sites; limited diversity.

CONCLUSION: An app-directed protocol for delirium identification was feasible, brief, and accurate, and CNAs and nurses performed as well as hospitalists.

PRIMARY FUNDING SOURCE: National Institute on Aging.

BACKGROUND: A positive delirium screen at skilled-nursing facility (SNF) admission can trigger a simultaneous diagnosis of Alzheimer's Disease or related dementia (AD/ADRD) and lead to psychoactive medication treatment despite a lack of evidence supporting use.

METHODS: This was a nationwide historical cohort study of 849,086 Medicare enrollees from 2011-2013 who were admitted to the SNF from a hospital without a history of dementia. Delirium was determined through positive Confusion Assessment Method screen and incident AD/ADRD through active diagnosis or claims. Cox proportional hazard models predicted the risk of receiving one of three psychoactive medications (i.e., antipsychotics, benzodiazepines, antiepileptics) within 7 days of SNF admission and within the entire SNF stay.

RESULTS: Of 849,086 newly-admitted SNF patients (62.6% female, mean age 78), 6.1% had delirium (of which 35.4% received an incident diagnosis of AD/ADRD); 12.6% received antipsychotics, 30.4% benzodiazepines, and 5.8% antiepileptics. Within 7 days of admission, patients with delirium and incident dementia were more likely to receive an antipsychotic (relative risk [RR] 3.09; 95% confidence interval [CI] 2.99 to 3.20), or a benzodiazepine (RR 1.23; 95% CI 1.19 to 1.27) than patients without either condition. By the end of the SNF stay, patients with both delirium and incident dementia were more likely to receive an antipsychotic (RR 3.04; 95% CI 2.95 to 3.14) and benzodiazepine (RR 1.32; 95% CI 1.29 to 1.36) than patients without either condition.

CONCLUSION: In this historical cohort, a positive delirium screen was associated with a higher risk of receiving psychoactive medication within 7 days of SNF admission, particularly in patients with an incident AD/ADRD diagnosis. Future research should examine strategies to reduce inappropriate psychoactive medication prescribing in older adults admitted with delirium to SNFs.

BACKGROUND: Postoperative delirium is frequent in older adults and is associated with postoperative neurocognitive disorder (PND). Studies evaluating perioperative medication use and delirium have generally evaluated medications in aggregate and been poorly controlled; the association between perioperative medication use and PND remains unclear. We sought to evaluate the association between medication use and postoperative delirium and PND in older adults undergoing major elective surgery.

METHODS: This is a secondary analysis of a prospective cohort study of adults ≥70 years without dementia undergoing major elective surgery. Patients were interviewed preoperatively to determine home medication use. Postoperatively, daily hospital use of 7 different medication classes listed in guidelines as risk factors for delirium was collected; administration before delirium was verified. While hospitalized, patients were assessed daily for delirium using the Confusion Assessment Method and a validated chart review method. Cognition was evaluated preoperatively and 1 month after surgery using a neurocognitive battery. The association between prehospital medication use and postoperative delirium was assessed using a generalized linear model with a log link function, controlling for age, sex, type of surgery, Charlson comorbidity index, and baseline cognition. The association between daily postoperative medication use (when class exposure ≥5%) and time to delirium was assessed using time-varying Cox models adjusted for age, sex, surgery type, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation (APACHE)-II score, and baseline cognition. Mediation analysis was utilized to evaluate the association between medication use, delirium, and cognitive change from baseline to 1 month.

RESULTS: Among 560 patients enrolled, 134 (24%) developed delirium during hospitalization. The multivariable analyses revealed no significant association between prehospital benzodiazepine (relative risk [RR], 1.44; 95% confidence interval [CI], 0.85-2.44), beta-blocker (RR, 1.38; 95% CI, 0.94-2.05), NSAID (RR, 1.12; 95% CI, 0.77-1.62), opioid (RR, 1.22; 95% CI, 0.82-1.82), or statin (RR, 1.34; 95% CI, 0.92-1.95) exposure and delirium. Postoperative hospital benzodiazepine use (adjusted hazard ratio [aHR], 3.23; 95% CI, 2.10-4.99) was associated with greater delirium. Neither postoperative hospital antipsychotic (aHR, 1.48; 95% CI, 0.74-2.94) nor opioid (aHR, 0.82; 95% CI, 0.62-1.11) use before delirium was associated with delirium. Antipsychotic use (either presurgery or postsurgery) was associated with a 0.34 point (standard error, 0.16) decrease in general cognitive performance at 1 month through its effect on delirium (P = .03), despite no total effect being observed.

CONCLUSIONS: Administration of benzodiazepines to older adults hospitalized after major surgery is associated with increased postoperative delirium. Association between inhospital, postoperative medication use and cognition at 1 month, independent of delirium, was not detected.

BACKGROUND: Delirium (an acute change in cognition) is a common, morbid, and costly syndrome seen primarily in aging adults. Despite increasing knowledge of its epidemiology, delirium remains a clinical diagnosis with no established biomarkers to guide diagnosis or management. Advances in proteomics now provide opportunities to identify novel markers of risk and disease progression for postoperative delirium and its associated long-term consequences (eg, long-term cognitive decline and Alzheimer's disease [AD]).

METHODS: In a nested matched case-control study (18 delirium/no-delirium pairs) within the Successful Aging after Elective Surgery study (N = 556), we evaluated the association of 1305 plasma proteins preoperatively [PREOP] and on postoperative day 2 [POD2]) with delirium using SOMAscan. Generalized linear models were applied to enzyme-linked immunosorbant assay (ELISA) validation data of one protein across the full cohort. Multi-protein modeling included delirium biomarkers identified in prior work (C-reactive protein, interleukin-6 [IL6]).

RESULTS: We identified chitinase-3-like-protein-1 (CHI3L1/YKL-40) as the sole delirium-associated protein in both a PREOP and a POD2 predictor model, a finding confirmed by ELISA. Multi-protein modeling found high PREOP CHI3L1/YKL-40 and POD2 IL6 increased the risk of delirium (relative risk [95% confidence interval] Quartile [Q]4 vs Q1: 2.4[1.2-5.0] and 2.1[1.1-4.1], respectively).

CONCLUSIONS: Our identification of CHI3L1/YKL-40 in postoperative delirium parallels reports of CHI3L1/YKL-40 and its association with aging, mortality, and age-related conditions including AD onset and progression. This highlights the type 2 innate immune response, involving CHI3L1/YKL-40, as an underlying mechanism of postoperative delirium, a common, morbid, and costly syndrome that threatens the independence of older adults.

Due to cost and participant burden, neuroimaging studies are often performed in relatively small samples of voluntary participants. This may lead to selection bias. It is important to identify factors associated with participation in neuroimaging studies and understand their effect on outcome measures. We investigated the effect of postoperative delirium on long-term (over 48 months) cognitive decline (LTCD) in 560 older surgical patients (≥ 70 years), including a nested MRI cohort (n = 146). We observed a discrepancy in the effect of delirium on cognitive decline as a function of MRI participation. Although overall difference in cognitive decline due to delirium was not greater than what might be expected due to chance (p = .21), in the non-MRI group delirium was associated with a faster pace of LTCD (-0.063, 95% CI -0.094 to -0.032, p < .001); while in the MRI group the effect of delirium was less and not significant (-0.023, 95% CI -0.076, 0.030, p = .39). Since this limits our ability to investigate the neural correlates of delirium and cognitive decline using MRI data, we attempted to mitigate the observed discrepancy using inverse probability weighting for MRI participation. The approach was not successful and the difference of the effect of delirium in slope was essentially unchanged. There was no evidence that the MRI sub-group experienced delirium that differed in severity relative to MRI non-participants. We could not attribute the observed discrepancy to selection bias based on measured factors. It may reflect a power issue due to the smaller MRI subsample or selection bias from unmeasured factors.

PURPOSE: The routine use of validated diagnostic instruments is key to identifying delirious patients early and expediting care. The 3-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM) instrument is a brief, easy to use, sensitive, and specific delirium assessment tool for hospitalized patients. We aimed to translate the original English version into French, and then adapt it to older high-risk patients.

METHODS: Translation and adaptation of the questionnaire were guided by an expert committee and the 3D-CAM instrument developer. During the translation phase, we achieved semantic and conceptual equivalence of the instrument by conducting forward and backward translations. During the adaptation phase, we assessed the face validity, clarity of wording, and ease of use of the translated questionnaire by administering it to 30 patients and their caregivers in peri-interventional and medical intermediate care units. During both phases, we used qualitative (goal and adequacy of the questionnaire) and quantitative (Sperber score, clarity score) criteria.

RESULTS: Translation: four items were judged inadequate and were revised until all reached a Sperber score of < 3/7. Face validity: 91% of patients thought the questionnaire was designed to assess memory, thoughts, or reasoning. Clarity: eight items required adjustments until all scored ≥ 9/10 for clarity. Ease of use: all bedside caregivers reported that the questionnaire was easy to complete after receiving brief instructions.

CONCLUSIONS: We produced a culturally adapted French version of the 3D-CAM instrument that is well understood and well-received by older high-risk patients and their caregivers.

IMPORTANCE: The ability to rate delirium severity is key to providing optimal care for older adults, and such ratings would allow clinicians to target patients with severe delirium and monitor response to treatment, recovery time, and prognosis; assess nursing burden and staffing needs; and, ultimately, provide more appropriate patient-centered care. Current delirium severity measures have been limited in their content, gradations, and measurement characteristics.

OBJECTIVE: To examine the internal consistency, reliability, and validity for clinical outcomes of the DEL-S delirium severity score, a measure of delirium severity that was developed using advanced psychometric approaches, analogous to those of the Patient-Reported Outcomes Measurement Information System initiative.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted at a large academic medical center in Boston, Massachusetts. Adults aged 70 years or older who were admitted or transferred to medical or surgical services as either emergency or elective admissions were enrolled between October 20, 2015, and March 15, 2017, and were monitored for 1 year. Data analysis was performed from June 2020 to August 2021.

EXPOSURES: Delirium severity, measured by scores on the delirium severity score short-form (SF; 6 items, scored 0-13, with higher scores indicating more severe delirium) and long-form (LF; 17 items, scored 0-21), considered continuously and grouped into 5 categories.

MAIN OUTCOMES AND MEASURES: The primary outcomes were in-hospital outcomes, including length of stay and hospital costs, and posthospital (30, 90, and 365 days) outcomes, including death, health care costs, and rehospitalization.

RESULTS: The 352 participants had a median (IQR) age of 79.7 (74.6-85.5) years, 204 (58.0%) were women, and they were highly educated (median [IQR] duration of education, 14 [7-20] years). Patients in the highest delirium severity score SF group (scores 6-9) had a longer length of stay (13.3 vs 6.9 days; P for trend < .001), greater in-hospital costs ($57 700 vs $34 200), greater cumulative health care costs ($168 700 vs $106 500; P for trend = .01), and increased mortality at 1 year (50% vs 17%; P for trend = .02) compared with patients in the lowest delirium severity score SF group (score 0). Similar trends and significant findings were demonstrated for the delirium severity score LF.

CONCLUSIONS AND RELEVANCE: These findings suggest that the delirium severity score provides an approach for measuring delirium severity that is associated with adverse clinical outcomes in a direct exposure-response association and that the delirium severity score may help advance patient-centered care for delirium.

Background: Delirium, an acute decline in attention and global cognitive dysfunction, occurs frequently following cardiac surgery and has been demonstrated to be significantly associated with cognitive dysfunction and reduced functional ability. In the DEXACET trial, we demonstrated a significant reduction in postoperative in-hospital delirium with intravenous (IV) acetaminophen when compared with placebo. In this analysis we examined whether this protective association also extended to 12 month cognitive and functional outcomes. Methods: This study was a prospective, randomized, placebo-controlled, triple-blinded, factorial design trial conducted at Beth Israel Deaconess Medical Center, approved by the IRB. In this trial, 120 older cardiac surgical patients were randomly assigned to receive either intravenous (IV) acetaminophen or placebo in addition to propofol or dexmedetomidine. Those receiving IV acetaminophen displayed a significant reduction in in-hospital delirium. We collected cognitive, mood and functional outcome data using the Montreal Cognitive Assessment, telephone version (T-MoCA), Geriatric Depression Scale (GDS) and the Basic and Instrumental Activities of Daily Living (ADLs, IADLs) at 1 month and 12 months after surgery. Results: Of the 120 enrolled patients in the primary trial, 93 (77.5%) and 83 (69.2%) patients responded to assessments at 1 month and 12 months, respectively. No statistically significant differences in median T-MoCA scores were observed between acetaminophen and placebo groups at 1 month (18.0 vs.18.0, p = 0.52) or 12 months (19.0 vs.18.0, p = 0.62) following surgery. There were similarly no differences in GDS, ADLs or IADLs between treatment groups. Losses to follow-up limited the sample sizes and 10 of the 23 (45%) original study participants who had postoperative delirium were lost to follow up. Conclusion: Administration of intravenous acetaminophen was not associated with a difference in long term cognitive or functional status following cardiac surgery. Additional research on long-term outcomes following postoperative delirium with a larger sample size and improved cohort retention strategies will be needed to address this important area.

BACKGROUND: Patients with dementia are frequently hospitalized and may face barriers in post-discharge care.

OBJECTIVE: To determine whether patients with dementia have an increased risk of adverse outcomes following discharge.

DESIGN: Retrospective cohort study.

SUBJECTS: Medicare beneficiaries hospitalized in 2016.

MAIN MEASURES: Co-primary outcomes were mortality and readmission within 30 days of discharge. Multivariable logistic regression models were estimated to assess the risk of each outcome for patients with and without dementia accounting for demographics, comorbidities, frailty, hospitalization factors, and disposition.

KEY RESULTS: The cohort included 1,089,109 hospitalizations of which 211,698 (19.3%) were of patients with diagnosed dementia (median (IQR) age 83 (76-89); 61.5% female) and 886,411 were of patients without dementia (median (IQR) age 76 (79-83); 55.0% female). At 30 days following discharge, 5.7% of patients with dementia had died compared to 3.1% of patients without dementia (adjusted odds ratio (aOR) 1.21; 95% CI 1.17 to 1.24). At 30 days following discharge, 17.7% of patients with dementia had been readmitted compared to 13.1% of patients without dementia (aOR 1.02; CI 1.002 to 1.04). Dementia was associated with an increased odds of readmission among patients discharged to the community (aOR 1.07, CI 1.05 to 1.09) but a decreased odds of readmission among patients discharge to nursing facilities (aOR 0.93, CI 0.90 to 0.95). Patients with dementia who were discharged to the community were more likely to be readmitted than those discharged to nursing facilities (18.9% vs 16.0%), and, when readmitted, were more likely to die during the readmission (20.7% vs 4.4%).

CONCLUSIONS: Diagnosed dementia was associated with a substantially increased risk of mortality and a modestly increased risk of readmission within 30 days of discharge. Patients with dementia discharged to the community had particularly elevated risk of adverse outcomes indicating possible gaps in post-discharge services and caregiver support.

BACKGROUND: Systematic screening can improve delirium identification among hospitalized older adults. Prior studies have shown clinicians and health system leaders may believe they do not have the time and resources for assessment. We conducted a comparative salary-related cost analysis of an adaptive delirium identification protocol directed by an iPad app.

METHODS: We recruited 527 older adult medicine patients from an urban academic medical center (n = 269) and a rural community hospital (n = 258). Physicians and nurses completed the two-step Ultra-brief Confusion Assessment Method (UB-CAM) protocol (with or without a skip pattern), while certified nursing assistants completed only the UB-2 ultra-brief screen. The sample included 527 patients (average age 80, 57% women, 35% with dementia). Time required to administer the protocol was collected automatically by the iPad app. Salary-related costs of screening were determined by multiplying the time required by the hourly wage for the three disciplines, as obtained from national and regional published healthcare salary cost data. Cost estimates for entire hospital implementation were also calculated.

RESULTS: Participants were screened on 924 hospital days by 399 clinicians (53 physicians, 236 nurses, 110 CNAs). For the UB-2, CNAs cost per screen was lower than the other clinician types ($0.37 per screen vs. $0.73 for nurses and $2.39 for hospitalists). For the UB-CAM with skip (UB-CAM), costs per protocol were $1.10 for nurses vs. $3.61 for physicians. The annual salary-related costs of hospital-wide implementation of a nurse-based UB-CAM protocol in a medium-sized (300-bed) hospital was $63,015 plus $4356 for initial and annual training.

CONCLUSIONS: CNAs and nurses had the lowest salary-associated costs for app-directed CAM-based delirium screening and identification, respectively. Salary-related annual hospital costs for the most efficient protocols in a medium-sized hospital were less than the annual cost of hiring 1 FTE of the discipline performing the protocols.