Medicare Transitional Care Management Program and Changes in Timely Postdischarge Follow-Up.

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.

Management of Inpatient Elevated Blood Pressures : A Systematic Review of Clinical Practice Guidelines.

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).

Trends in observation stays for Medicare beneficiaries with and without Alzheimer's disease and related dementias.

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.

The Delphi Delirium Management Algorithms. A practical tool for clinicians, the result of a modified Delphi expert consensus approach.

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.

Biomarkers of neurodegeneration and neural injury as potential predictors for delirium.

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 (Aß)42 , Aß40 , total (t)-Tau, phosphorylated (p)-Tau181 , 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, Aß40 and Aß42 . 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.

Factors associated with disagreement between clinician app-based ultra-brief Confusion Assessment Method and reference standard delirium assessments.

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.

Successful aging after elective surgery II: Study cohort description.

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.

Long-term Outcomes with Spinal versus General Anesthesia for Hip Fracture Surgery: A Randomized Trial.

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.

Association of Loneliness With Change in Physical and Emotional Health of Older Adults During the COVID-19 Shutdown.

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.

Comparison of the frailty index and frailty phenotype and their associations with postoperative delirium incidence and severity.

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.

Aptamer-Based Proteomics Measuring Preoperative Cerebrospinal Fluid Protein Alterations Associated with Postoperative Delirium.

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.

Application of Multiple Omics to Understand Postoperative Delirium Pathophysiology in Humans.

Delirium, an acute change in cognition, is common, morbid, and costly, particularly among hospitalized older adults. Despite growing knowledge of its epidemiology, far less is known about delirium pathophysiology. Initial work understanding delirium pathogenesis has focused on assaying single or a limited subset of molecules or genetic loci. Recent technological advances at the forefront of biomarker and drug target discovery have facilitated application of multiple "omics" approaches aimed to provide a more complete understanding of complex disease processes such as delirium. At its basic level, "omics" involves comparison of genes (genomics, epigenomics), transcripts (transcriptomics), proteins (proteomics), metabolites (metabolomics), or lipids (lipidomics) in biological fluids or tissues obtained from patients who have a certain condition (i.e., delirium) and those who do not. Multi-omics analyses of these various types of molecules combined with machine learning and systems biology enable the discovery of biomarkers, biological pathways, and predictors of delirium, thus elucidating its pathophysiology. This review provides an overview of the most recent omics techniques, their current impact on identifying delirium biomarkers, and future potential in enhancing our understanding of delirium pathogenesis. We summarize challenges in identification of specific biomarkers of delirium and, more importantly, in discovering the mechanisms underlying delirium pathophysiology. Based on mounting evidence, we highlight a heightened inflammatory response as one common pathway in delirium risk and progression, and we suggest other promising biological mechanisms that have recently emerged. Advanced multiple omics approaches coupled with bioinformatics methodologies have great promise to yield important discoveries that will advance delirium research.

Trends in use of antipsychotics and psychoactive drugs in older patients after major surgery.

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.

Comparative Safety Analysis of Oral Antipsychotics for In-Hospital Adverse Clinical Events in Older Adults After Major Surgery : A Nationwide Cohort Study.

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.

Role of Blood-Brain Barrier Dysfunction in Delirium following Non-cardiac Surgery in Older Adults.

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.

Trends in healthy days at home for Medicare beneficiaries using the emergency department.

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.

The association between gut microbiota and postoperative delirium in patients.

Postoperative delirium is a common postoperative complication in older patients, and its pathogenesis and biomarkers remain largely undetermined. The gut microbiota has been shown to regulate brain function, and therefore, it is vital to explore the association between gut microbiota and postoperative delirium. Of 220 patients (65 years old or older) who had a knee replacement, hip replacement, or laminectomy under general or spinal anesthesia, 86 participants were included in the data analysis. The incidence (primary outcome) and severity of postoperative delirium were assessed for two days. Fecal swabs were collected from participants immediately after surgery. The 16S rRNA gene sequencing was used to assess gut microbiota. Principal component analyses along with a literature review were used to identify plausible gut microbiota, and three gut bacteria were further studied for their associations with postoperative delirium. Of the 86 participants [age 71.0 (69.0-76.0, 25-75% percentile of quartile), 53% female], 10 (12%) developed postoperative delirium. Postoperative gut bacteria Parabacteroides distasonis was associated with postoperative delirium after adjusting for age and sex (Odds Ratio [OR] 2.13, 95% Confidence Interval (CI): 1.09-4.17, P = 0.026). The association between delirium and both Prevotella (OR: 0.59, 95% CI: 0.33-1.04, P = 0.067) and Collinsella (OR: 0.57, 95% CI: 0.27-1.24, P = 0.158) did not meet statistical significance. These findings suggest that there may be an association between postoperative gut microbiota, specifically Parabacteroides distasonis, and postoperative delirium. However, further research is needed to confirm these findings and better understand the gut-brain axis's role in postoperative outcomes.

Outcomes with spinal versus general anesthesia for patients with and without preoperative cognitive impairment: Secondary analysis of a randomized clinical trial.

INTRODUCTION: The effect of spinal versus general anesthesia on the risk of postoperative delirium or other outcomes for patients with or without cognitive impairment (including dementia) is unknown. METHODS: Post hoc secondary analysis of a multicenter pragmatic trial comparing spinal versus general anesthesia for adults aged 50 years or older undergoing hip fracture surgery. RESULTS: Among patients randomized to spinal versus general anesthesia, new or worsened delirium occurred in 100/295 (33.9%) versus 107/283 (37.8%; odds ratio [OR] 0.85; 95% confidence interval [CI] 0.60 to 1.19) among persons with cognitive impairment and 70/432 (16.2%) versus 71/445 (16.0%) among persons without cognitive impairment (OR 1.02; 95% CI 0.71 to 1.47, p = 0.46 for interaction). Delirium severity, in-hospital complications, and 60-day functional recovery did not differ by anesthesia type in patients with or without cognitive impairment. DISCUSSION: Anesthesia type is not associated with differences in delirium and functional outcomes among persons with or without cognitive impairment.

Clinical Outcomes of Intensive Inpatient Blood Pressure Management in Hospitalized Older Adults.

Importance: Asymptomatic blood pressure (BP) elevations are common in hospitalized older adults, and widespread heterogeneity in the clinical management of elevated inpatient BPs exists. Objective: To examine the association of intensive treatment of elevated inpatient BPs with in-hospital clinical outcomes of older adults hospitalized for noncardiac conditions. Design, Setting, and Participants: This retrospective cohort study examined Veterans Health Administration data between October 1, 2015, and December 31, 2017, for patients aged 65 years or older hospitalized for noncardiovascular diagnoses and who experienced elevated BPs in the first 48 hours of hospitalization. Interventions: Intensive BP treatment following the first 48 hours of hospitalization, defined as receipt of intravenous antihypertensives or oral classes not used prior to admission. Main Outcome and Measures: The primary outcome was a composite of inpatient mortality, intensive care unit transfer, stroke, acute kidney injury, B-type natriuretic peptide elevation, and troponin elevation. Data were analyzed between October 1, 2021, and January 10, 2023, with propensity score overlap weighting used to adjust for confounding between those who did and did not receive early intensive treatment. Results: Among 66 140 included patients (mean [SD] age, 74.4 [8.1] years; 97.5% male and 2.6% female; 17.4% Black, 1.7% Hispanic, and 75.9% White), 14 084 (21.3%) received intensive BP treatment in the first 48 hours of hospitalization. Patients who received early intensive treatment vs those who did not continued to receive a greater number of additional antihypertensives during the remainder of their hospitalization (mean additional doses, 6.1 [95% CI, 5.8-6.4] vs 1.6 [95% CI, 1.5-1.8], respectively). Intensive treatment was associated with a greater risk of the primary composite outcome (1220 [8.7%] vs 3570 [6.9%]; weighted odds ratio [OR], 1.28; 95% CI, 1.18-1.39), with the highest risk among patients receiving intravenous antihypertensives (weighted OR, 1.90; 95% CI, 1.65-2.19). Intensively treated patients were more likely to experience each component of the composite outcome except for stroke and mortality. Findings were consistent across subgroups stratified by age, frailty, preadmission BP, early hospitalization BP, and cardiovascular disease history. Conclusions and Relevance: The study's findings indicate that among hospitalized older adults with elevated BPs, intensive pharmacologic antihypertensive treatment was associated with a greater risk of adverse events. These findings do not support the treatment of elevated inpatient BPs without evidence of end organ damage, and they highlight the need for randomized clinical trials of inpatient BP treatment targets.

A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults.

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, 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 postoperative change 0.28, [IQR] [-0.48-1.24]; Wilcoxon p=0.001). Preoperative to 24-hour postoperative change in CPAR was greater among patients who developed delirium vs those who did not (median [IQR] 1.31 [0.004, 2.34] vs 0.19 [-0.55, 1.08]; p=0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24-hour postoperative change in CPAR was independently associated with delirium incidence (per CPAR increase of 1, OR = 1.30, [95% CI 1.03-1.63]; p=0.026) and increased hospital length of stay (IRR = 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.