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Aarti Rao,1 Sandra M Shi,2,3 Jonathan Afilalo,4 Jeffrey J Popma,5 Kamal R Khabbaz,6 Roger J Laham,5 Kimberly Guibone,5 Edward R Marcantonio,2,7,* Dae Hyun Kim2,3,* 1Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 3Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA; 4Division of Cardiology and Centre for Clinical Epidemiology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; 5Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 6Division of Cardiac Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA; 7Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA*These authors contributed equally to this workCorrespondence: Dae Hyun KimHinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA 02131, USATel +1 617-971-8320Fax +1 617-971-5339Email daehyunkim@hsl.harvard.eduBackground: Delirium is a major risk factor for poor recovery after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). It is unclear whether preoperative physical performance tests improve delirium prediction.Objective: To examine whether physical performance tests can predict delirium after SAVR and TAVR, and adapt an existing delirium prediction rule for cardiac surgery, which includes Mini-Mental State Examination (MMSE), depression, prior stroke, and albumin level.Design: Prospective cohort, 2014– 2017.Setting: Single academic center.Subjects: A total of 187 patients undergoing SAVR (n=77) or TAVR (n=110).Methods: The Short Physical Performance Battery (SPPB) score was calculated based on gait speed, balance, and chair stands (range: 0– 12 points, lower scores indicate poor performance). Delirium was assessed using the Confusion Assessment Method. We fitted logistic regression to predict delirium using SPPB components and risk factors of delirium.Results: Delirium occurred in 35.8% (50.7% in SAVR and 25.5% in TAVR). The risk of delirium increased for lower SPPB scores: 10– 12 (28.2%), 7– 9 (34.5%), 4– 6 (37.5%) and 0– 3 (44.1%) (p-for-trend=0.001). A model that included gait speed < 0.46 meter/second (OR, 2.7; 95% CI, 1.2– 6.4), chair stands time ≥ 11.2 seconds (OR, 3.5; 95% CI, 1.0– 12.4), MMSE < 24 points (OR, 2.9; 95% CI, 1.3– 6.4), isolated SAVR (OR, 5.4; 95% CI, 2.1– 13.8), and SAVR and coronary artery bypass grafting (OR, 15.8; 95% CI, 5.5– 45.7) predicted delirium better than the existing prediction rule (C statistics: 0.71 vs 0.61; p=0.035).Conclusion: Assessing physical performance, in addition to cognitive function, can help identify high-risk patients for delirium after SAVR and TAVR.Keywords: delirium, physical performance, aortic valve replacement, prediction

ContextRight heart catheterization (RHC) is commonly performed before high-risk noncardiac surgery, but the benefit of this strategy remains unproven.ObjectiveTo evaluate the relationship between use of perioperative RHC and postoperative cardiac complication rates in patients undergoing major noncardiac surgery.DesignProspective, observational cohort study.SettingTertiary care teaching hospital in the United States.PatientsPatients (n = 4059 aged >/=50 years) who underwent major elective noncardiac procedures with an expected length of stay of 2 or more days between July 18, 1989, and February 28, 1994. Two hundred twenty one patients had RHC and 3838 did not.Main outcome measureCombined end point of major postoperative cardiac events, including myocardial infarction, unstable angina, cardiogenic pulmonary edema, ventricular fibrillation, documented ventricular tachycardia or primary cardiac arrest, and sustained complete heart block, classified by a reviewer blinded to preoperative data.ResultsMajor cardiac events occurred in 171 patients (4.2%). Patients who underwent perioperative RHC had a 3-fold increase in incidence of major postoperative cardiac events (34 [15.4%] vs 137 [3.6%]; P

BackgroundCardiac complications are important causes of morbidity after noncardiac surgery. The purpose of this prospective cohort study was to develop and validate an index for risk of cardiac complications.Methods and resultsWe studied 4315 patients aged > or = 50 years undergoing elective major noncardiac procedures in a tertiary-care teaching hospital. The main outcome measures were major cardiac complications. Major cardiac complications occurred in 56 (2%) of 2893 patients assigned to the derivation cohort. Six independent predictors of complications were identified and included in a Revised Cardiac Risk Index: high-risk type of surgery, history of ischemic heart disease, history of congestive heart failure, history of cerebrovascular disease, preoperative treatment with insulin, and preoperative serum creatinine >2.0 mg/dL. Rates of major cardiac complication with 0, 1, 2, or > or = 3 of these factors were 0.5%, 1.3%, 4%, and 9%, respectively, in the derivation cohort and 0.4%, 0.9%, 7%, and 11%, respectively, among 1422 patients in the validation cohort. Receiver operating characteristic curve analysis in the validation cohort indicated that the diagnostic performance of the Revised Cardiac Risk Index was superior to other published risk-prediction indexes.ConclusionsIn stable patients undergoing nonurgent major noncardiac surgery, this index can identify patients at higher risk for complications. This index may be useful for identification of candidates for further risk stratification with noninvasive technologies or other management strategies, as well as low-risk patients in whom additional evaluation is unlikely to be helpful.

PurposeTo describe the relationship of body mass index (BMI) with postoperative complications and resource utilization.Patients and methodsTwo thousand nine hundred and sixty-four patients 50 years or older undergoing elective noncardiac surgery with an expected length of stay > or = 2 days were enrolled in a prospective cohort study to measure major cardiac complications, noncardiac complications, length of stay, and costs. The setting was an urban teaching hospital. A preoperative history, physical, electrocardiogram (ECG), and chart review were performed by study personnel. Postoperative complications were detected by ECGs, creatine kinase and creatine kinase MB levels, and daily chart review. Total costs were obtained from the hospital's computerized database.ResultsComplication rates were not different among BMI groups (underweight < 20, normal 20 to 29, overweight 30 to 34, most overweight > 34), but patients with BMI 30 to 34 and > 34 who underwent abdominal or gynecologic procedures had significantly higher wound infection rates (11% each) than normal weight patients (4.7%) or the underweight (0%). After adjusting for age, race, gender, smoking history, comorbid diseases, procedure type, and insurance status, there were nonsignificant trends toward increased resource utilization by the most overweight patients (BMI > 34). These patients stayed 0.8 days longer (P = 0.13) and had total costs that were $843 higher (P = 0.17) than patients of normal weight (BMI 20 to 29). The underweight patients stayed 0.9 days longer (P = 0.23) and had total costs that were $3,150 higher (P = 0.04) than patients of normal weight. Quadratic models to test for a U-shaped relationship found no correlation between BMI and length of stay, but did find that BMI was significantly correlated with total costs (P = 0.04). This relationship persisted when patients who had complications were excluded from the analysis.ConclusionsOverall, BMI was not significantly correlated with postoperative complications or length of stay. However, overweight patients who underwent abdominal or gynecologic procedures had higher wound infection rates, and patients with the highest and lowest BMIs had significantly higher adjusted total costs.

Delirium (acute confusion) complicates 15% to 50% of major operations in older adults and is associated with other major postoperative complications, prolonged length of stay, poor functional recovery, institutionalization, dementia, and death. Importantly, delirium may be predictable and preventable through proactive intervention. Yet clinicians fail to recognize and address postoperative delirium in up to 80% of cases. Using the case of Ms R, a 76-year-old woman who developed delirium first after colectomy with complications and again after routine surgery, the diagnosis, prevention, and treatment of delirium in the postoperative setting is reviewed. The risk of postoperative delirium can be quantified by the sum of predisposing and precipitating factors. Successful strategies for prevention and treatment of delirium include proactive multifactorial intervention targeted to reversible risk factors, limiting use of sedating medications (especially benzodiazepines), effective management of postoperative pain, and, perhaps, judicious use of antipsychotics. [ABSTRACT FROM AUTHOR]

Background: Increased peak postoperative B-type natriuretic peptide (BNP) is associated with increased major adverse cardiovascular events and all-cause mortality after coronary artery bypass graft (CABG) surgery. Whether increased postoperative BNP predicts worse postdischarge physical function (PF) is unknown. We hypothesized that peak postoperative BNP associates with PF assessed up to 2 yr after CABG surgery, even after adjusting for clinical risk factors. including preoperative PF.Methods: This two-institution prospective cohort study included patients undergoing primary CABG surgery with cardiopulmonary bypass. Short Form-36 questionnaires were administered to subjects preoperatively and 6 months, 1 yr, and 2 yr postoperatively. Short Form-36 PF domain scores were calculated using the Short Form-36 norm-based scoring algorithm. Plasma BNP concentrations measured preoperatively and on postoperative days 1-5 were log(10) transformed before analysis. To determine whether peak postoperative BNP independently predicts PF scores 6 months through 2 yr after CABG surgery, multivariable longitudinal regression analysis of the postoperative PF scores was performed, adjusting for important clinical risk factors.Results: A total of 845 subjects (mean ± SD age, 65 ± 10 yr) were analyzed. Peak postoperative BNP was significantly associated with postoperative PF (effect estimate for log(10) peak BNP, -7.66 PF score points [95% CI, -9.68 to -5.64]; P = <0.0001). After multivariable adjustments, peak postoperative BNP remained independently associated with postoperative PF (effect estimate for log(10) peak BNP, -3.06 PF score points [95% CI, -5.15 to -0.97]; P = 0.004).Conclusions: Increased peak postoperative BNP independently associates with worse longer-term PF after primary CABG surgery. Future studies are needed to determine whether medical management targeted toward reducing increased postoperative BNP can improve PF after CABG surgery. [ABSTRACT FROM AUTHOR]

Cognitive and brain reserve are well studied in the context of age-associated cognitive impairment and dementia. However, there is a paucity of research that examines the role of cognitive or brain reserve in delirium. Indicators (or proxy measures) of cognitive or brain reserve (such as brain size, education, and activities) pose challenges in the context of the long prodromal phase of Alzheimer disease but are diminished in the context of delirium, which is of acute onset. This article provides a review of original articles on cognitive and brain reserve across many conditions affecting the central nervous system, with a focus on delirium. The authors review current definitions of reserve. The authors identify indicators for reserve used in earlier studies and discuss these indicators in the context of delirium. The authors highlight future research directions to move the field ahead. Reserve may be a potentially modifiable characteristic. Studying the role of reserve in delirium can advance prevention strategies for delirium and may advance knowledge of reserve and its role in aging and neuropsychiatric disease generally. [ABSTRACT FROM AUTHOR]

Background: Delirium is common among hospitalized elders and may persist for months. Therefore, the adverse impact of delirium on independence often occurs in the post acute care (PAC) setting. The effect of psychomotor subtypes on delirium remains uncertain. The purpose of this study is to examine the association between psychomotor activity delirium subtypes and 1-year mortality among 457 newly admitted delirious PAC patients.Methods: Patients were screened for delirium on admission to PAC facilities after an acute hospitalization, and patients with "Confusion Assessment Method"-defined delirium were enrolled. Psychomotor activity was assessed using the Memorial Delirium Assessment Scale, and patients were classified as to their delirium subtype (hyperactive, hypoactive, mixed, or normal). One-year mortality data were obtained from the National Death Index. A Kaplan-Meier survival analysis and a proportional hazards analysis using indicator (dummy) variables with normal psychomotor activity as the referent were performed.Results: The normal psychomotor activity group had the lowest 1-year mortality rate, followed by the hyperactive, mixed, then hypoactive groups in increasing order. Independent of age, gender, comorbidity, dementia, and delirium severity, hypoactive patients were 1.60 (95% confidence interval [CI], 1.09-2.35) times more likely to die during the 1-year follow-up period than were patients with normal psychomotor activity. The hyperactive (hazard ratio = 1.30; 95% CI, 0.73-2.31) and mixed (hazard ratio = 1.25; 95% CI, 0.72-2.17) psychomotor groups had nonsignificant elevated risks relative to the normal psychomotor behavior group.Conclusions: All three psychomotor disturbance subtypes had an elevated risk of dying during the 1-year follow-up relative to the normal psychomotor group, though the hypoactive group had the highest mortality risk and was the only group with a statistically significantly elevated risk relative to the normal group. [ABSTRACT FROM AUTHOR]

Background: Delirium is costly, common, and may persist for weeks or months. Therefore, the adverse impact of delirium on loss of independence may occur in the post-acute setting rather than in the hospital. The purpose of this study is to describe the rate of delirium persistence and identify baseline patient characteristics that are associated with delirium persistence at 1 month among newly admitted post-acute facility patients who were admitted with delirium.Methods: Patients were recruited from 4 Boston area skilled nursing facilities specializing in post-acute care (PAC). Assessment instruments included the Confusion Assessment Method Diagnostic Algorithm, the modified Delirium Symptom Interview, the Memorial Delirium Assessment Scale (MDAS), and the Blessed Dementia Rating Scale (BDRS). Multiple logistic regression analyses were used to identify patient characteristics associated with delirium persistence (at 1 month).Results: Nearly 51% of the 85 delirious patients enrolled in this study had delirium at their 1-month follow-up assessment. Four patient factors associated with delirium persistence were identified: older age (> or =85 years), severe delirium at PAC admission (MDAS score >15), prehospital cognitive impairment based on proxy report [BDRS], and the presence of all 8 modified Delirium Symptom Interview symptoms at PAC admission. Our model has very good predictive power (area under the receiver operating characteristic = 0.85).Conclusions: Delirium is persistent in the post-acute setting. If verified in further research, the risk factors found in this study could be used to identify patients who are likely to have delirium after 1 month, and may prove useful in developing and targeting interventions of care. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the association between the prevalence of delirium among patients admitted to postacute care and the quality of nursing home care as reflected in deficiency counts. DESIGN: Analysis of screening data from a randomized controlled trial (RCT) of a delirium abatement program. SETTING AND PARTICIPANTS: We screened 4744 of 6352 RCT-eligible persons admitted to 1 of 8 skilled nursing facilities in the Boston area over a 3-year period. Quality of care was operationalized with the count of deficiencies noted by state surveyors. MEASUREMENTS: Prevalence of Confusion Assessment Method (CAM) diagnoses of delirium as completed by trained research interviewers at each facility. RESULTS: About 1 in 7 persons admitted to postacute care met CAM criteria for delirium, but this varied from 1 in 15 to 1 in 4 across facilities. The correlation of deficiency count per 100 beds and the prevalence of CAM delirium was strong (r=0.45) and significant (95% Confidence interval =0.07, 0.71). CONCLUSION: Although this study is limited by small sample size, limited geographic scope, and crude assessment of quality with deficiency counts, we have found that facilities with more deficiencies admit more persons that satisfy CAM criteria for delirium. It is possible that good facilities often choose to admit and/or are referred good candidates for rehabilitation, whereas facilities with more deficiencies are not able to be so selective. The end result may be that delirious patients are being preferentially admitted to poorer quality facilities, increasing their likelihood of poor postacute outcomes. [ABSTRACT FROM AUTHOR]

Background: Although the pathogenesis of delirium is poorly understood, increasing evidence supports a role for inflammation. Previously, individual inflammatory biomarkers have been associated with delirium. Aggregating biomarkers into an index may provide more information than individual biomarkers in predicting certain health outcomes (e.g., mortality); however, inflammatory indices have not yet been examined in delirium., Methods: Four inflammatory markers, C-reactive protein, Interleukin-6, Soluble Tumor Necrosis Factor Alpha Receptor-1, and Chitinase-3 Like Protein-1 (CHI3L1), were measured preoperatively (PREOP) and on postoperative day 2 (POD2) in 548 adults aged 70+ undergoing major noncardiac surgery (mean age 76.7 [standard deviation 5.2], 58% female, 24% delirium). From these markers, four inflammatory indices were considered: 1) quartile summary score, 2) weighted summary score (WSS), 3) principal component score, 4) a well-established inflammatory (LASSO-derived) index associated with mortality. Delirium was assessed using the Confusion Assessment Method (CAM), supplemented by chart review. Generalized linear models (GLM) with a log-link term were used to determine the association between each inflammatory index and delirium incidence., Results: Among the inflammatory indices, WSS demonstrated the strongest association with delirium: participants in WSS quartile (Q)4 had a higher risk of delirium vs. participants in Q1, after clinical variable adjustment (relative risk [RR], 95% confidence interval [CI] for PREOP: 3.07, 1.80-5.22; and POD2: 2.65, 1.63-4.30). WSS was more strongly associated with delirium than the strongest associated individual inflammatory marker (PREOP CHI3L1 [RR 2.45, 95% CI 1.53-3.92]; POD2 interleukin-6 [RR 2.39, 95% CI 1.50-3.82])., Conclusions: A multi-protein inflammatory index using WSS provides a slight advantage over individual inflammatory markers in their association with delirium., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Delirium commonly occurs in older adults following surgery; although its pathophysiology is not fully understood, underlying neurodegeneration is a risk factor., Objective: Examine the association of preoperative levels of markers of neuronal damage, neurofilament light (NfL) and phosphorylated tau (p-tau) 181 , with postoperative delirium., Methods: Preoperative CSF and plasma were obtained from 158 patients undergoing hip fracture repair and enrolled in the clinical trial "A STrategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients" (STRIDE). Delirium diagnosis was adjudicated by a consensus panel. The association of plasma and CSF NfL and p-tau 181 levels with delirium incidence and severity were examined for the overall cohort and for the subgroup (n=134) of patients without dementia., Results: Patients who developed delirium were older, had lower Mini-Mental State Exam (MMSE) score, higher Clinical Dementia Rating (CDR) and Geriatric Depression Scale (GDS) scores at baseline; the overall incidence of delirium was 37.6% and 31.1% for the subgroup without dementia. Plasma and CSF p-tau 181 levels were not associated with delirium incidence or severity. CSF NfL levels were significantly associated with delirium severity, but not with incidence in the overall cohort. In the subgroup of patients without dementia, CSF NfL levels were significantly associated with increased odds of delirium incidence (OR 4.74, 95% CI 1.21-18.59, p=0.03) adjusted for age, sex, and CDR., Conclusions: CSF NfL was significantly associated with delirium incidence and severity in patients without dementia undergoing hip fracture repair. Results confirm prior studies suggesting NfL as an important marker of delirium risk and supports an association between pre-existing axonal injury and delirium. These results highlight delirium vulnerability in older hip fracture patients, even when clinical dementia is not identified., (Copyright © 2024 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Whether cognitive and functional recovery in skilled nursing facilities (SNF) following hospitalization differs by delirium and Alzheimer's disease related dementias (ADRD) has not been examined., Objective: To compare change in cognition and function among short-stay SNF patients with delirium, ADRD, or both., Design: Retrospective cohort study using claims data from 2011 to 2013., Setting: Centers for Medicare and Medicaid certified SNFs., Participants: A total of 740,838 older adults newly admitted to a short-stay SNF without prevalent ADRD who had at least two assessments of cognition and function., Measurements: Incident delirium was measured by the Minimum Data Set (MDS) Confusion Assessment Method and ICD-9 codes, and incident ADRD by ICD-9 codes and MDS diagnoses. Cognitive improvement was a better or maximum score on the MDS Brief Interview for Mental Status, and functional recovery was a better or maximum score on the MDS Activities of Daily Living Scale., Results: Within 30 days of SNF admission, the rate of cognitive improvement in patients with both delirium/ADRD was half that of patients with neither delirium/ADRD (HR = 0.45, 95% CI:0.43, 0.46). The ADRD-only and delirium-only groups also were 43% less likely to have improved cognition or function compared to those with neither delirium/ADRD (HR = 0.57, 95% CI:0.56, 0.58 and HR = 0.57, 95% CI:0.55, 0.60, respectively). Functional improvement was less likely in patients with both delirium/ADRD, as well (HR = 0.85, 95% CI:0.83, 0.87). The ADRD only and delirium only groups were also less likely to improve in function (HR = 0.93, 95% CI:0.92, 0.94 and HR = 0.92, 95% CI:0.90, 0.93, respectively) compared to those with neither delirium/ADRD., Conclusions: Among older adults without dementia admitted to SNF for post-acute care following hospitalization, a positive screen for delirium and a new diagnosis of ADRD, within 7 days of SNF admission, were both significantly associated with worse cognitive and functional recovery. Patients with both delirium and new ADRD had the worst cognitive and functional recovery., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background: Postoperative delirium is the most common complication following surgery among older adults, and has been consistently associated with increased mortality and morbidity, cognitive decline, and loss of independence, as well as markedly increased health-care costs. Electroencephalography (EEG) spectral slowing has frequently been observed during episodes of delirium, whereas intraoperative frontal alpha power is associated with postoperative delirium. We sought to identify preoperative predictors that could identify individuals at high risk for postoperative delirium, which could guide clinical decision-making and enable targeted interventions to potentially decrease delirium incidence and postoperative delirium-related complications., Methods: In this prospective observational study, we used machine learning to evaluate whether baseline (preoperative) cognitive function and resting-state EEG could be used to identify patients at risk for postoperative delirium. Preoperative resting-state EEGs and the Montreal Cognitive Assessment were collected from 85 patients (age = 73 ± 6.4 years, 12 cases of delirium) undergoing elective surgery. The model with the highest f1-score was subsequently validated in an independent, prospective cohort of 51 older adults (age = 68 ± 5.2 years, 6 cases of delirium) undergoing elective surgery., Results: Occipital alpha powers have higher f1-score than frontal alpha powers and EEG spectral slowing in the training cohort. Occipital alpha powers were able to predict postoperative delirium with AUC, specificity and accuracy all >90%, and sensitivity >80%, in the validation cohort. Notably, models incorporating transformed alpha powers and cognitive scores outperformed models incorporating occipital alpha powers alone or cognitive scores alone., Conclusions: While requiring prospective validation in larger cohorts, these results suggest that strong prediction of postoperative delirium may be feasible in clinical settings using simple and widely available clinical tools. Additionally, our results suggested that the thalamocortical circuit exhibits different EEG patterns under different stressors, with occipital alpha powers potentially reflecting baseline vulnerabilities., Competing Interests: Dr. E. Santarnecchi serves on the scientific advisory boards for BottNeuro, which has no overlap with present work; and is listed as an inventor on several issued and pending patents on brain stimulation solutions to diagnose or treat neurodegenerative disorders and brain tumors. Dr. A. Pascual-Leone is a co-founder of Linus Health and TI Solutions AG which have no overlap with present work. He serves on the scientific advisory boards for the ACE Foundation and the IT’IS Foundation, Neuroelectrics, TetraNeuron, Skin2Neuron, MedRhythms, and Magstim Inc; and is listed as an inventor on several issued and pending patents on the real-time integration of noninvasive brain stimulation with electroencephalography and magnetic resonance imaging, applications of noninvasive brain stimulation in various neurological disorders, as well as digital biomarkers of cognition and digital assessments for early diagnosis of dementia. Dr. M Berger has received private legal consulting fees related to perioperative neurocognitive disorders. None of the other authors report any conflicts of interest. All the other co-authors fully disclose they have no financial interests, activities, relationships and affiliations. The other co-authors also declare they have no potential conflicts in the three years prior to submission of this manuscript.

Background: Increased intraoperative electroencephalographic (EEG) burst suppression is associated with postoperative delirium. Cerebral desaturation is considered as one of the factors associated with burst suppression. Our study investigates the association between cerebral desaturation and burst suppression by analyzing their concurrence. Additionally, we aim to examine their association with cardiac surgical phases to identify potential for targeted interventions., Methods: We retrospectively analyzed intraoperative 1-minute interval observations in 51 patients undergoing cardiac surgery. Processed EEG and cerebral oximetry were collected, with the anesthesiologists blinded to the information. The associations between cerebral desaturation (defined as a 10% decrease from baseline) and burst suppression, as well as with phase of cardiac surgery, were analyzed using the Generalized Logistic Mixed Effect Model. The results were presented as odds ratio and 95% confidence intervals (CIs). A value of P < .05 was considered statistically significant., Results: The odds of burst suppression increased 1.5 times with cerebral desaturation (odds ratio [OR], 1.52, 95% CI, 1.11-2.07; P = .009). Compared to precardiopulmonary bypass (pre-CPB), the odds of cerebral desaturation were notably higher during CPB (OR, 22.1, 95% CI, 12.4-39.2; P < .001) and post-CPB (OR, 18.2, 95% CI, 12.2-27.3; P < .001). However, the odds of burst suppression were lower during post-CPB (OR, 0.69, 95% CI, 0.59-0.81; P < .001) compared to pre-CPB. Compared to pre-CPB, the odds of concurrent cerebral desaturation and burst suppression were notably higher during CPB (OR, 52.3, 95% CI, 19.5-140; P < .001) and post-CPB (OR, 12.7, 95% CI, 6.39-25.2; P < .001). During CPB, the odds of cerebral desaturation (OR, 6.59, 95% CI, 3.62-12; P < .001) and concurrent cerebral desaturation and burst suppression (OR, 10, 95% CI, 4.01-25.1; P < .001) were higher in the period between removal of aortic cross-clamp and end of CPB. During the entire surgery, the odds of burst suppression increased 8 times with higher inhalational anesthesia concentration (OR, 7.81, 95% CI, 6.26-9.74; P < .001 per 0.1% increase)., Conclusions: Cerebral desaturation is associated with intraoperative burst suppression during cardiac surgery, most significantly during CPB, especially during the period between the removal of the aortic cross-clamp and end of CPB. Further exploration with simultaneous cerebral oximetry and EEG monitoring is required to determine the causes of burst suppression. Targeted interventions to address cerebral desaturation may assist in mitigating burst suppression and consequently enhance postoperative cognitive function., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 International Anesthesia Research Society.)

Importance: Despite guidelines recommending avoidance of benzodiazepine administration to older patients, many of them now receive benzodiazepines as a part of anesthesia care. The effectiveness of clinician- and patient-facing interventions to discourage such use remains insufficiently characterized., Objective: To evaluate the effect of clinician peer comparison, patient informational mail, or a combination of these interventions compared with usual care on the rate of perioperative benzodiazepine administration to older patients., Design, Setting, and Participants: This 2 × 2 factorial, stepped-wedge, cluster randomized clinical trial of a corporate quality improvement initiative was conducted between August 8, 2022, and May 28, 2023, across 415 hospitals, surgery centers, and physician offices in 8 US states served by anesthesia clinicians from a national anesthesia practice. Participants were adults aged 65 years or older who underwent an elective surgical or endoscopic procedure with general anesthesia. Data analyses followed the intention-to-treat principle., Intervention: Patients were randomly assigned to 1 of 4 groups-clinician peer comparison (wherein clinicians received feedback regarding their performance compared with other clinicians in the practice), patient informational mail (wherein patients received an informational letter encouraging them to have a discussion regarding medication selection with their clinician on the day of surgery), both interventions, or usual care (no intervention)., Main Outcomes and Measures: Rate of benzodiazepine administration during anesthesia care and patient satisfaction with anesthesia care (measured by the Anesthesia Patient Satisfaction Questionnaire, version 2)., Results: Among the 509 269 enrolled participants (255 871 females [50.2%]; mean [SD] age, 74 [7] years), 81 363 (16.0%) were assigned to clinician peer comparison, 98 520 (19.3%) to patient informational mail, 169 712 (33.3%) to both interventions, and 159 674 (31.4%) to usual care. Among patients who received benzodiazepine during anesthesia care, 24.5% were in the usual care group compared with 19.7% in the clinician peer comparison group, 20.0% in the patient informational mail group, and 19.7% in the combination group. After adjustment for time, none of the study interventions were associated with lower odds of benzodiazepine administration compared with usual care (odds ratio [OR], 1.02 [95% CI, 0.98-1.07]; P = .35 for clinician peer comparison; OR, 1.01 [95% CI, 0.96-1.05]; P = .81 for patient informational mail; and OR, 1.11 [95% CI, 1.05-1.16]; P < .001 for combined interventions). Satisfaction scores were high in all groups and did not vary by treatment assignment., Conclusions and Relevance: This randomized clinical trial found that clinician peer comparison, patient informational mail, or a combination of both interventions did not reduce benzodiazepine administration to older patients compared with usual care; patient satisfaction remained high throughout the study. Overall, the findings suggest a need to explore other patient-targeted interventions to improve anesthesia care., Trial Registration: Clinicaltrials.gov Identifier: NCT05436392.

Background: Timely follow-up after cardiovascular hospitalization is recommended to monitor recovery, titrate medications, and coordinate care., Objective: To describe trends and disparities in follow-up after acute myocardial infarction (AMI) and heart failure (HF) hospitalizations., Design: Retrospective cohort study., Setting: Medicare., Participants: Medicare fee-for-service beneficiaries hospitalized between 2010 and 2019., Measurements: Receipt of a cardiology visit within 30 days of discharge. Multivariable logistic regression models were used to estimate changes over time overall and across 5 sociodemographic characteristics on the basis of known disparities in cardiovascular outcomes., Results: The cohort included 1 678 088 AMI and 4 245 665 HF hospitalizations. Between 2010 and 2019, the rate of cardiology follow-up increased from 48.3% to 61.4% for AMI hospitalizations and from 35.2% to 48.3% for HF hospitalizations. For both conditions, follow-up rates increased for all subgroups, yet disparities worsened for Hispanic patients with AMI and patients with HF who were Asian, Black, Hispanic, Medicaid dual eligible, and residents of counties with higher levels of social deprivation. By 2019, the largest disparities were between Black and White patients (AMI, 51.9% vs. 59.8%, difference, 7.9 percentage points [pp] [95% CI, 6.8 to 9.0 pp]; HF, 39.8% vs. 48.7%, difference, 8.9 pp [CI, 8.2 to 9.7 pp]) and Medicaid dual-eligible and non-dual-eligible patients (AMI, 52.8% vs. 60.4%, difference, 7.6 pp [CI, 6.9 to 8.4 pp]; HF, 39.7% vs. 49.4%, difference, 9.6 pp [CI, 9.2 to 10.1 pp]). Differences between hospitals explained 7.3 pp [CI, 6.7 to 7.9 pp] of the variation in follow-up for AMI and 7.7 pp [CI, 7.2 to 8.1 pp]) for HF., Limitation: Generalizability to other payers., Conclusion: Equity-informed policy and health system strategies are needed to further reduce gaps in follow-up care for patients with AMI and patients with HF., Primary Funding Source: National Institute on Aging., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-3475.

In older patients, delirium after surgery is associated with long-term cognitive decline (LTCD). The neural substrates of this association are unclear. Neurodegenerative changes associated with dementia are possible contributors. We investigated the relationship between brain atrophy rates in Alzheimer's disease (AD) and cognitive aging signature regions from magnetic resonance imaging before and one year after surgery, LTCD assessed by the general cognitive performance (GCP) score over 6 years post-operatively, and delirium in 117 elective surgery patients without dementia (mean age = 76). The annual change in cortical thickness was 0.2(1.7) % (AD-signature p = 0.09) and 0.4(1.7) % (aging-signature p = 0.01). Greater atrophy was associated with LTCD (AD-signature: beta(CI) = 0.24(0.06-0.42) points of GCP/mm of cortical thickness; p < 0.01, aging-signature: beta(CI) = 0.55(0.07-1.03); p = 0.03). Atrophy rates were not significantly different between participants with and without delirium. We found an interaction with delirium severity in the association between atrophy and LTCD (AD-signature: beta(CI) = 0.04(0.00-0.08), p = 0.04; aging-signature: beta(CI) = 0.08(0.03-0.12), p < 0.01). The rate of cortical atrophy and severity of delirium are independent, synergistic factors determining postoperative cognitive decline in the elderly., Competing Interests: Competing Interests Dr. Dickerson has been a consultant for Acadia, Alector, Arkuda, Biogen, Denali, Genentech, Lilly, Merck, Novartis, Takeda, Wave Lifesciences, and has received royalties from Cambridge University Press, Elsevier, Oxford University Press. Other authors have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Preoperative risk biomarkers for delirium may aid in identifying high-risk patients and developing intervention therapies, which would minimize the health and economic burden of postoperative delirium. Previous studies have typically used single omics approaches to identify such biomarkers. Preoperative cerebrospinal fluid (CSF) from the Healthier Postoperative Recovery study of adults ≥ 63 years old undergoing elective major orthopedic surgery was used in a matched pair delirium case-no delirium control design. We performed metabolomics and lipidomics, which were combined with our previously reported proteomics results on the same samples. Differential expression, clustering, classification, and systems biology analyses were applied to individual and combined omics datasets. Probabilistic graph models were used to identify an integrated multi-omics interaction network, which included clusters of heterogeneous omics interactions among lipids, metabolites, and proteins. The combined multi-omics signature of 25 molecules attained an AUC of 0.96 [95% CI: 0.85-1.00], showing improvement over individual omics-based classification. We conclude that multi-omics integration of preoperative CSF identifies potential risk markers for delirium and generates new insights into the complex pathways associated with delirium. With future validation, this hypotheses-generating study may serve to build robust biomarkers for delirium and improve our understanding of its pathophysiology.

Background: Recent studies have reported an association between presurgical frailty and postoperative delirium. However, it remains unclear whether the frailty-delirium relationship differs by measurement tool (e.g., frailty index vs. frailty phenotype) and whether frailty is associated with delirium, independent of preoperative cognition., Methods: We used the successful aging after elective surgery (SAGES) study, a prospective cohort of older adults age ≥70 undergoing major non-cardiac surgery (N = 505). Preoperative measurement of the modified mini-mental (3MS) test, frailty index and frailty phenotype were obtained. The confusion assessment method (CAM), supplemented by chart review, identified postoperative delirium. Delirium feature severity was measured by the sum of CAM-severity (CAM-S) scores. Generalized linear models were used to determine the relative risk of each frailty measure with delirium incidence and severity. Subsequent models adjusted for age, sex, surgery type, Charlson comorbidity index, and 3MS., Results: On average, patients were 76.7 years old (standard deviation 5.22), 58.8% of women. For the frailty index, the incidence of delirium was 14% in robust, 17% in prefrail, and 31% in frail patients (p < 0.001). For the frailty phenotype, delirium incidence was 13% in robust, 21% in prefrail, and 27% in frail patients (p = 0.016). Frailty index, but not phenotype, was independently associated with delirium after adjustment for comorbidities (relative risk [RR] 2.13, 95% confidence interval [CI] 1.23-3.70; RR 1.61, 95% CI 0.77-3.37, respectively). Both frailty measures were associated with delirium feature severity. After adjustment for preoperative cognition, only the frailty index was associated with delirium incidence; neither index nor phenotype was associated with delirium feature severity., Conclusion: Both the frailty index and phenotype were associated with the development of postoperative delirium. The index showed stronger associations that remained significant after adjusting for baseline comorbidities and preoperative cognition. Measuring frailty prior to surgery can assist in identifying patients at risk for postoperative delirium., (© 2023 The American Geriatrics Society.)

Background: There has been a marked rise in the use of observation care for Medicare beneficiaries visiting the emergency department (ED) in recent years. Whether trends in observation use differ for people with Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) is unknown., Methods: Using a national 20% sample of Medicare beneficiaries ages 68+ from 2012 to 2018, we compared trends in ED visits and observation stays by AD/ADRD status for beneficiaries visiting the ED. We then examined the degree to which trends differed by nursing home (NH) residency status, assigning beneficiaries to four groups: AD/ADRD residing in NH (AD/ADRD+ NH+), AD/ADRD not residing in NH (AD/ADRD+ NH-), no AD/ADRD residing in NH (AD/ADRD- NH+), and no AD/ADRD not residing in NH (AD/ADRD- NH-)., Results: Of 7,489,780 unique beneficiaries, 18.6% had an AD/ADRD diagnosis. Beneficiaries with AD/ADRD had more than double the number of ED visits per 1000 in all years compared to those without AD/ADRD and saw a faster adjusted increase over time (+26.7 vs. +8.2 visits/year; p < 0.001 for interaction). The annual increase in the adjusted proportion of ED visits ending in observation was also greater among people with AD/ADRD (+0.78%/year, 95% CI 0.77-0.80%) compared to those without AD/ADRD (+0.63%/year, 95% CI 0.59-0.66%; p < 0.001 for interaction). Observation utilization was greatest for the AD/ADRD+ NH+ population and lowest for the AD/ADRD- NH- population, but the AD/ADRD+ NH- group saw the greatest increase in observation stays over time (+15.4 stays per 1000 people per year, 95% CI 15.0-15.7)., Conclusions: Medicare beneficiaries with AD/ADRD have seen a disproportionate increase in observation utilization in recent years, driven by both an increase in ED visits and an increase in the proportion of ED visits ending in observation., (© 2024 The American Geriatrics Society.)

Importance: In 2013, Medicare implemented payments for transitional care management (TCM) services, which provide increased reimbursement to clinicians providing ambulatory care to patients after discharge from medical facilities to the community., Objective: To determine whether the introduction of TCM payments was associated with an increase in timely postdischarge follow-up., Design, Setting, and Participants: This cross-sectional interrupted time-series study assessed quarterly postdischarge visit rates before (2010-2012) and after (2013-2019) TCM implementation 100% sample of Medicare fee-for-service beneficiaries discharged to the community after a hospital or skilled nursing facility stay. Data analyses were performed February 1 to December 15, 2023., Exposure: Implementation of payments for TCM., Main Outcomes and Measures: Timely postdischarge primary care follow-up, defined as receipt of a primary care ambulatory visit within 14 days of discharge. Secondary outcomes included receipt of a TCM visit and specialty care follow-up., Results: The study sample comprised 79 125 965 eligible discharges. Of these, 55.4% were female; 1.5% were Asian, 12.1% Black, 5.6% Hispanic, and 79.0% were White individuals; and 79.6% were beneficiaries aged 65 years and older. Timely primary care follow-up increased from 31.5% in 2010 to 38.8% in 2019 (absolute increase 7.3%), whereas specialist follow-up increased from 27.6% to 30.8% (absolute increase 3.2%). By 2019, 11.3% of eligible patients received TCM services. Interrupted time-series analyses demonstrated an increased slope of timely primary care follow-up after the introduction of TCM services (pre-TCM slope, 0.12% per quarter vs post-TCM slope, 0.29% per quarter; difference, 0.13%; 95% CI, 0.02% to 0.22%). Receipt of timely follow-up increased for all demographic groups; however, Black, Hispanic, and Medicaid dual-eligible patients and patients residing in urban areas and counties with high-level social deprivation were less likely to receive follow-up during the study period. These disparities widened for Black patients (difference-in-differences in pre-TCM vs post-TCM slope, -0.14%; 95% CI, -0.25% to -0.2%) and patients who were Medicaid dual-eligible (difference-in-differences pre-TCM vs post-TCM slope, -0.21%; 95% CI, -0.35% to -0.07%)., Conclusions: These findings indicate that Medicare's introduction of payments for TCM services was associated with a persistent increase in the rate of timely postdischarge primary care but did not narrow demographic or socioeconomic disparities. Most beneficiaries did not receive timely primary care follow-up.

Background: Management of elevated blood pressure (BP) during hospitalization varies widely, with many hospitalized adults experiencing BPs higher than those recommended for the outpatient setting., Purpose: To systematically identify guidelines on elevated BP management in the hospital., Data Sources: MEDLINE, Guidelines International Network, and specialty society websites from 1 January 2010 to 29 January 2024., Study Selection: Clinical practice guidelines pertaining to BP management for the adult and older adult populations in ambulatory, emergency department, and inpatient settings., Data Extraction: Two authors independently screened articles, assessed quality, and extracted data. Disagreements were resolved via consensus. Recommendations on treatment targets, preferred antihypertensive classes, and follow-up were collected for ambulatory and inpatient settings., Data Synthesis: Fourteen clinical practice guidelines met inclusion criteria (11 were assessed as high-quality per the AGREE II [Appraisal of Guidelines for Research & Evaluation II] instrument), 11 provided broad BP management recommendations, and 1 each was specific to the emergency department setting, older adults, and hypertensive crises. No guidelines provided goals for inpatient BP or recommendations for managing asymptomatic moderately elevated BP in the hospital. Six guidelines defined hypertensive urgency as BP above 180/120 mm Hg, with hypertensive emergencies requiring the addition of target organ damage. Hypertensive emergency recommendations consistently included use of intravenous antihypertensives in intensive care settings. Recommendations for managing hypertensive urgencies were inconsistent, from expert consensus, and focused on the emergency department. Outpatient treatment with oral medications and follow-up in days to weeks were most often advised. In contrast, outpatient BP goals were clearly defined, varying between 130/80 and 140/90 mm Hg., Limitation: Exclusion of non-English-language guidelines and guidelines specific to subpopulations., Conclusion: Despite general consensus on outpatient BP management, guidance on inpatient management of elevated BP without symptoms is lacking, which may contribute to variable practice patterns., Primary Funding Source: National Institute on Aging. (PROSPERO: CRD42023449250)., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-3251.

Background: Recently, the Ultra-Brief Confusion Assessment Method (UB-CAM), designed to help physicians and nurses to recognize delirium, showed high, but imperfect, accuracy compared with Research Reference Standard Delirium Assessments (RRSDAs). The aim of this study is to identify factors associated with disagreement between clinicians' app-based UB-CAM assessments and RRSDAs., Methods: This is a secondary analysis of a prospective diagnostic test study. The study was conducted at two hospitals and included 527 inpatients (≥70 years old) and 289 clinicians (53 physicians, 236 nurses). Trained research associates performed RRSDAs and determined delirium presence using the CAM. Clinicians administered the UB-CAM using an iPad app. Disagreement factors considered were clinician, patient, and delirium characteristics. We report odds ratios and 95% confidence intervals., Results: One thousand seven hundred and ninety-five clinician UB-CAM assessments paired with RRSDAs were administered. The prevalence of delirium was 17%. The rate of disagreement between clinician UB-CAM assessments and RRSDAs was 12%. Significant factors associated with disagreement between clinician UB-CAM assessments and RRSDAs (OR [95% CI]) included: presence of dementia (2.7 [1.8-4.1]), patient education high school or less (1.9 [1.3-2.9]), psychomotor retardation (2.5 [1.4-4.2]), and the presence of mild delirium or subsyndromal delirium (5.5 [3.5-8.7]). Significant risk factors for false negatives were patient age less than 80 (2.2 [1.1-4.3]) and mild delirium (3.5 [1.6-7.4]). Significant risk factors for false positives were presence of dementia (4.0 [2.3-7.0]), subsyndromal delirium (5.1 [2.9-9.1]), and patient education high school or less (2.0 [1.2-3.6]). Clinician characteristics were not significantly associated with disagreement., Conclusions: The strongest factors associated with disagreement between clinician UB-CAM screens and RRSDAs were the presence of dementia and subsyndromal delirium as risk factors for false positives, and mild delirium and younger age as a risk factor for false negatives. These disagreement factors contrast with previous studies of risk factors for incorrect clinician delirium screening, and better align screening results with patient outcomes., (© 2023 The American Geriatrics Society.)

Background: The effects of spinal versus general anesthesia on long-term outcomes have not been well studied. This study tested the hypothesis that spinal anesthesia is associated with better long-term survival and functional recovery than general anesthesia., Methods: A prespecified analysis was conducted of long-term outcomes of a completed randomized superiority trial that compared spinal anesthesia versus general anesthesia for hip fracture repair. Participants included previously ambulatory patients 50 yr of age or older at 46 U.S. and Canadian hospitals. Patients were randomized 1:1 to spinal or general anesthesia, stratified by sex, fracture type, and study site. Outcome assessors and investigators involved in the data analysis were masked to the treatment arm. Outcomes included survival at up to 365 days after randomization (primary); recovery of ambulation among 365-day survivors; and composite endpoints for death or new inability to ambulate and death or new nursing home residence at 365 days. Patients were included in the analysis as randomized., Results: A total of 1,600 patients were enrolled between February 12, 2016, and February 18, 2021; 795 were assigned to spinal anesthesia, and 805 were assigned to general anesthesia. Among 1,599 patients who underwent surgery, vital status information at or beyond the final study interview (conducted at approximately 365 days after randomization) was available for 1,427 (89.2%). Survival did not differ by treatment arm; at 365 days after randomization, there were 98 deaths in patients assigned to spinal anesthesia versus 92 deaths in patients assigned to general anesthesia (hazard ratio, 1.08; 95% CI, 0.81 to 1.44, P = 0.59). Recovery of ambulation among patients who survived a year did not differ by type of anesthesia (adjusted odds ratio for spinal vs. general, 0.87; 95% CI, 0.67 to 1.14; P = 0.31). Other outcomes did not differ by treatment arm., Conclusions: Long-term outcomes were similar with spinal versus general anesthesia., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit., Competing Interests: DISCLOSURES The authors have no conflicts of interest to disclose.

Background: The Successful Aging after Elective Surgery (SAGES) II Study was designed to examine the relationship between delirium and Alzheimer's disease and related dementias (AD/ADRD), by capturing novel fluid biomarkers, neuroimaging markers, and neurophysiological measurements. The goal of this paper is to provide the first complete description of the enrolled cohort, which details the baseline characteristics and data completion. We also describe the study modifications necessitated by the COVID-19 pandemic, and lay the foundation for future work using this cohort., Methods: SAGES II is a prospective observational cohort study of community-dwelling adults age 65 and older undergoing major non-cardiac surgery. Participants were assessed preoperatively, throughout hospitalization, and at 1, 2, 6, 12, and 18 months following discharge to assess cognitive and physical functioning. Since participants were enrolled throughout the COVID-19 pandemic, procedural modifications were designed to reduce missing data and allow for high data quality., Results: About 420 participants were enrolled with a mean (standard deviation) age of 73.4 (5.6) years, including 14% minority participants. Eighty-eight percent of participants had either total knee or hip replacements; the most common surgery was total knee replacement with 210 participants (50%). Despite the challenges posed by the COVID-19 pandemic, which required the use of novel procedures such as video assessments, there were minimal missing interviews during hospitalization and up to 1-month follow-up; nearly 90% of enrolled participants completed interviews through 6-month follow-up., Conclusion: While there are many longitudinal studies of older adults, this study is unique in measuring health outcomes following surgery, along with risk factors for delirium through the application of novel biomarkers-including fluid (plasma and cerebrospinal fluid), imaging, and electrophysiological markers. This paper is the first to describe the characteristics of this unique cohort and the data collected, enabling future work using this novel and important resource., (© 2023 The American Geriatrics Society.)

Objectives: Determine if biomarkers of Alzheimer's disease and neural injury may play a role in the prediction of delirium risk., Methods: In a cohort of older adults who underwent elective surgery, delirium case-no delirium control pairs (N = 70, or 35 matched pairs) were matched by age, sex and vascular comorbidities. Biomarkers from CSF and plasma samples collected prior to surgery, including amyloid beta (Aβ) 42 , Aβ 40 , total (t)-Tau, phosphorylated (p)-Tau 181 , neurofilament-light (NfL), and glial fibrillary acid protein (GFAP) were measured in cerebrospinal fluid (CSF) and plasma using sandwich enzyme-linked immunosorbent assays (ELISAs) or ultrasensitive single molecule array (Simoa) immunoassays., Results: Plasma GFAP correlated significantly with CSF GFAP and both plasma and CSF GFAP values were nearly two-fold higher in delirium cases. The median paired difference between delirium case and control without delirium for plasma GFAP was not significant (p = 0.074) but higher levels were associated with a greater risk for delirium (odds ratio 1.52, 95% confidence interval 0.85, 2.72 per standard deviation increase in plasma GFAP concentration) in this small study. No matched pair differences or associations with delirium were observed for NfL, p-Tau 181, Aβ 40 and Aβ 42 ., Conclusions: These preliminary findings suggest that plasma GFAP, a marker of astroglial activation, may be worth further investigation as a predictive risk marker for delirium., (© 2023 John Wiley & Sons Ltd.)

Background: Professional society guidelines recommend limiting the use of antipsychotics in older patients with postoperative delirium. How these recommendations affected the use of antipsychotics and other psychoactive drugs in the postoperative period has not been studied., Methods: This retrospective cohort study included patients 65 years or older without psychiatric diagnoses who underwent major surgery in community hospitals (CHs) and academic medical centers (AMCs) in the United States. The outcome was the rate of hospital days exposed to antipsychotics, antidepressants, antiepileptics, benzodiazepines, hypnotics, and selective alpha-2 receptor agonist dexmedetomidine in the postoperative period by hospital type., Results: The study included 4,098,431 surgical admissions from CHs (mean age 75.0 [standard deviation, 7.1] years; 50.8% female) during 2008-2018 and 2,310,529 surgical admissions from AMCs (75.0 [7.4] years; 49.4% female) during 2009-2018. In the intensive care unit (ICU) setting, the number of exposed days per 1000 hospital-days declined for haloperidol (CHs: 33-21 days [p < 0.01]; AMCs: 24-15 days [p < 0.01]) and benzodiazepines (CHs: 261-136 days [p < 0.01]; AMCs: 150-77 days [p < 0.01]). The use of atypical antipsychotics, antidepressants, antiepileptics, and dexmedetomidine increased, while hypnotic use varied by the hospital type. In the non-ICU setting, the rate declined for haloperidol in CHs but not in AMCs (CHs: 10-6 days [p < 0.01]; AMCs: 4-3 days [p = 0.52]) and for benzodiazepines in both settings (CHs: 126-56 days [p < 0.01]; AMCs: 30-27 days [p < 0.01]). The use of antiepileptics and antidepressants increased, while the use of atypical antipsychotics and hypnotics varied by the hospital type., Conclusions: The use of haloperidol and benzodiazepines in the postoperative period declined at both CHs and AMCs. These trends coincided with the increasing use of other psychoactive drugs., (© 2023 The American Geriatrics Society.)

Objectives: To examine factors influencing loneliness and the effect of loneliness on physical and emotional health, in the context of the COVID-19 pandemic., Design: Prospective, observational cohort., Setting: Community-dwelling participants., Participants: Older adults (n = 238) enrolled in a longitudinal study., Measurements: Interviews were completed July-December 2020. Loneliness was measured with the UCLA 3-item loneliness scale. Data including age, marriage, education, cognitive functioning, functional impairment, vision or hearing impairment, depression, anxiety, medical comorbidity, social network size, technology use, and activity engagement were collected. Health outcomes included self-rated health, and physical and mental composites from the 12-item Short Form Survey. Physical function was measured by a PROMIS-scaled composite score., Results: Thirty-nine (16.4%) participants reported loneliness. Vulnerability factors for loneliness included age (RR = 1.08, 95% CI 1.02-1.14); impairment with instrumental activities of daily living (RR = 2.08, 95% CI 1.14-3.80); vision impairment (RR = 2.09, 95% CI 1.10-3.97); depression (RR = 1.34, 95% CI 1.25-1.43); and anxiety (RR = 1.92, 95% CI 1.55-2.39). Significant resilience factors included high cognitive functioning (RR = 0.88, 95% CI 0.83-0.94); large social network size (RR = 0.92, 95% CI 0.88-0.96); technology use (RR = 0.81, 95% CI 0.73-0.90); and social and physical activity engagement (RR = 0.91, 95% CI 0.85-0.98). Interaction analyses showed that larger social network size moderated the effect of loneliness on physical function (protective interaction effect, RR = 0.64, 95% CI 0.15-1.13, p <.01), and activity engagement moderated the effect of loneliness on mental health (protective interaction effect, RR = 0.65, 95% CI 0.25-1.05, p <.001)., Conclusions: Resilience factors may mitigate the adverse health outcomes associated with loneliness. Interventions to enhance resilience may help to diminish the detrimental effects of loneliness and hold great importance for vulnerable older adults., (Published by Elsevier Inc.)

Objective: Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients., Methods: Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery. Blood-brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR)., Results: Of 207 patients (median age = 68 years, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24 hours after surgery (median change = 0.28, interquartile range [IQR] = -0.48 to 1.24, Wilcoxon p = 0.001). Preoperative to 24 hours postoperative change in CPAR was greater among patients who developed delirium versus those who did not (median [IQR] = 1.31 [0.004 to 2.34] vs 0.19 [-0.55 to 1.08], p = 0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24 hours postoperative change in CPAR was independently associated with delirium occurrence (per CPAR increase of 1, odds ratio = 1.30, 95% confidence interval [CI] = 1.03-1.63, p = 0.026) and increased hospital length of stay (incidence rate ratio = 1.15, 95% CI = 1.09-1.22, p < 0.001)., Interpretation: Postoperative increases in blood-brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood-brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay. ANN NEUROL 2023;94:1024-1035., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Older adults, particularly those with Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD), have high rates of emergency department (ED) visits and are at risk for poor outcomes. How best to measure quality of care for this population has been debated. Healthy Days at Home (HDAH) is a broad outcome measure reflecting mortality and time spent in facility-based healthcare settings versus home. We examined trends in 30-day HDAH for Medicare beneficiaries after visiting the ED and compared trends by AD/ADRD status., Methods: We identified all ED visits among a national 20% sample of Medicare beneficiaries ages 68 and older from 2012 to 2018. For each visit, we calculated 30-day HDAH by subtracting mortality days and days spent in facility-based healthcare settings within 30 days of an ED visit. We calculated adjusted rates of HDAH using linear regression, accounting for hospital random effects, visit diagnosis, and patient characteristics. We compared rates of HDAH among beneficiaries with and without AD/ADRD, including accounting for nursing home (NH) residency status., Results: We found fewer adjusted 30-day HDAH after ED visits among patients with AD/ADRD compared to those without AD/ADRD (21.6 vs. 23.0). This difference was driven by a greater number of mortality days, SNF days, and, to a lesser degree, hospital observation days, ED visits, and long-term hospital days. From 2012 to 2018, individuals living with AD/ADRD had fewer HDAH each year but a greater mean annual increase over time (p < 0.001 for the interaction between year and AD/ADRD status). Being a NH resident was associated with fewer adjusted 30-day HDAH for beneficiaries with and without AD/ADRD., Conclusions: Beneficiaries with AD/ADRD had fewer HDAH following an ED visit but saw moderately greater increases in HDAH over time compared to those without AD/ADRD. This trend was visit driven by declining mortality and utilization of inpatient and post-acute care., (© 2023 The American Geriatrics Society.)

Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to a lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover and investigate candidate protein biomarkers in preoperative CSF that were associated with the development of postoperative delirium in older surgical patients. We employed a nested case-control study design coupled with high multiplex affinity proteomics analysis to measure 1305 proteins in preoperative CSF. Twenty-four matched delirium cases and non-delirium controls were selected from the Healthier Postoperative Recovery (HiPOR) cohort, and the associations between preoperative protein levels and postoperative delirium were assessed using t -test statistics with further analysis by systems biology to elucidate delirium pathophysiology. Proteomics analysis identified 32 proteins in preoperative CSF that significantly associate with delirium ( t -test p < 0.05). Due to the limited sample size, these proteins did not remain significant by multiple hypothesis testing using the Benjamini-Hochberg correction and q-value method. Three algorithms were applied to separate delirium cases from non-delirium controls. Hierarchical clustering classified 40/48 case-control samples correctly, and principal components analysis separated 43/48. The receiver operating characteristic curve yielded an area under the curve [95% confidence interval] of 0.91 [0.80-0.97]. Systems biology analysis identified several key pathways associated with risk of delirium: inflammation, immune cell migration, apoptosis, angiogenesis, synaptic depression and neuronal cell death. Proteomics analysis of preoperative CSF identified 32 proteins that might discriminate individuals who subsequently develop postoperative delirium from matched control samples. These proteins are potential candidate biomarkers for delirium and may play a role in its pathophysiology.

Background: Antipsychotics are commonly used to manage postoperative delirium. Recent studies reported that haloperidol use has declined, and atypical antipsychotic use has increased over time., Objective: To compare the risk for in-hospital adverse events associated with oral haloperidol, olanzapine, quetiapine, and risperidone in older patients after major surgery., Design: Retrospective cohort study., Setting: U.S. hospitals in the Premier Healthcare Database., Patients: 17 115 patients aged 65 years and older without psychiatric disorders who were prescribed an oral antipsychotic drug after major surgery from 2009 to 2018., Interventions: Haloperidol (≤4 mg on the day of initiation), olanzapine (≤10 mg), quetiapine (≤150 mg), and risperidone (≤4 mg)., Measurements: The risk ratios (RRs) for in-hospital death, cardiac arrhythmia events, pneumonia, and stroke or transient ischemic attack (TIA) were estimated after propensity score overlap weighting., Results: The weighted population had a mean age of 79.6 years, was 60.5% female, and had in-hospital death of 3.1%. Among the 4 antipsychotics, quetiapine was the most prescribed (53.0% of total exposure). There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%, reference group), olanzapine (2.8%; RR, 0.74 [95% CI, 0.42 to 1.27]), quetiapine (2.6%; RR, 0.70 [CI, 0.47 to 1.04]), and risperidone (3.3%; RR, 0.90 [CI, 0.53 to 1.41]). The risk for nonfatal clinical events ranged from 2.0% to 2.6% for a cardiac arrhythmia event, 4.2% to 4.6% for pneumonia, and 0.6% to 1.2% for stroke or TIA, with no statistically significant differences by treatment group., Limitation: Residual confounding by delirium severity; lack of untreated group; restriction to oral low-to-moderate dose treatment., Conclusion: These results suggest that atypical antipsychotics and haloperidol have similar rates of in-hospital adverse clinical events in older patients with postoperative delirium who receive an oral low-to-moderate dose antipsychotic drug., Primary Funding Source: National Institute on Aging., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3021.