A Mediation Analysis Examining High Risk, Anticholinergic Medication Use, Delirium, and Dementia After Major Surgery.

INTRODUCTION: Anticholinergic medications are known to cause adverse cognitive effects in community-dwelling older adults and medical inpatients, including dementia. The prevalence with which such medications are prescribed in older adults undergoing major surgery is not well described nor is their mediating relationship with delirium and dementia. We sought to determine the prevalence of high-risk medication use in major surgery patients and their relationship with the subsequent development of dementia. METHODS: This was a retrospective cohort study which used data between January 2013 and December 2019, in a large midwestern health system, including sixteen hospitals. All patients over age 50 undergoing surgery requiring an inpatient stay were included. The primary exposure was the number of doses of anticholinergic medications delivered during the hospital stay. The primary outcome was a new diagnosis of Alzheimer's disease and related dementias at 1-y postsurgery. Regression methods and a mediation analysis were used to explore relationships between anticholinergic medication usage, delirium, and dementia. RESULTS: There were 39,665 patients included, with a median age of 66. Most patients were exposed to anticholinergic medications (35,957/39,665; 91%), and 7588/39,665 (19.1%) patients received six or more doses during their hospital stay. Patients with at least six doses of these medications were more likely to be female, black, and with a lower American Society of Anesthesiologists class. Upon adjusted analysis, high doses of anticholinergic medications were associated with increased odds of dementia at 1 y relative to those with no exposure (odds ratio 2.7; 95% confidence interval 2.2-3.3). On mediation analysis, postoperative delirium mediated the effect of anticholinergic medications on dementia, explaining an estimated 57.6% of their association. CONCLUSIONS: High doses of anticholinergic medications are common in major surgery patients and, in part via a mediating relationship with postoperative delirium, are associated with the development of dementia 1 y following surgery. Strategies to decrease the use of these medications and encourage the use of alternatives may improve long-term cognitive recovery.

A world-wide study on delirium assessments and presence of protocols.

BACKGROUND: Delirium is a common complication of older people in hospitals, rehabilitation and long-term facilities. OBJECTIVE: To assess the worldwide use of validated delirium assessment tools and the presence of delirium management protocols. DESIGN: Secondary analysis of a worldwide one-day point prevalence study on World Delirium Awareness Day, 15 March 2023. SETTING: Cross-sectional online survey including hospitals, rehabilitation and long-term facilities. METHODS: Participating clinicians reported data on delirium, the presence of protocols, delirium assessments, delirium-awareness interventions, non-pharmacological and pharmacological interventions, and ward/unit-specific barriers. RESULTS: Data from 44 countries, 1664 wards/units and 36 048 patients were analysed. Validated delirium assessments were used in 66.7% (n = 1110) of wards/units, 18.6% (n = 310) used personal judgement or no assessment, and 10% (n = 166) used other assessment methods. A delirium management protocol was reported in 66.8% (n = 1094) of wards/units. The presence of protocols for delirium management varied across continents, ranging from 21.6% (on 21/97 wards/units) in Africa to 90.4% (235/260) in Australia, similar to the use of validated delirium assessments with 29.6% (29/98) in Africa to 93.5% (116/124) in North America. Wards/units with a delirium management protocol [n = 1094/1664, 66.8%] were more likely to use a validated delirium test than those without a protocol [odds ratio 6.97 (95% confidence interval 5.289-9.185)]. The presence of a delirium protocol increased the chances for valid delirium assessment and, likely, evidence-based interventions. CONCLUSION: Wards/units that reported the presence of delirium management protocols had a higher probability of using validated delirium assessments tools to assess for delirium.

Advancing specificity in delirium: The delirium subtyping initiative.

BACKGROUND: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HIGHLIGHTS: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.

Nursing science at Mayo Clinic: An alternative model to traditional hospital-based nurse scientist positions.

The role of the Nurse Scientist in clinical settings represents a relatively new career path that has garnered attention in recent literature. Although there is considerable variability in how this role is operationalized across institutions, Mayo Clinic stands out as one of the few health systems in the United States employing nurse scientists who are fully and exclusively engaged in their own programs of research. Given the need for practical information to guide development and implementation of a research-focused nurse scientist role, the purpose of this paper is to describe the infrastructure and resources supporting Mayo Clinic nurse scientists, share role expectations and metrics for success, discuss both the facilitators of success and ongoing challenges, and compare our current practices to those found in the literature.

Perioperative ischaemic brain injury and plasma neurofilament light: a secondary analysis of two prospective cohort studies.

BACKGROUND: Ischaemic brain infarction can occur without acute neurological symptoms (covert strokes) or with symptoms (overt strokes), both associated with poor health outcomes. We conducted a pilot study of the incidence of preoperative and postoperative (intraoperative or postoperative) covert strokes, and explored the relationship of postoperative ischaemic brain injury to blood levels of neurofilament light, a biomarker of neuronal damage. METHODS: We analysed 101 preoperative (within 2 weeks of surgery) and 58 postoperative research MRIs on postoperative days 2-9 from two prospective cohorts collected at the University of Wisconsin (NCT01980511 and NCT03124303). Participants were aged >65 yr and undergoing non-intracranial, non-carotid surgery. RESULTS: Preoperative covert stroke was identified in 2/101 participants (2%; Bayesian 95% confidence interval [CI], 0.2-5.4). This rate was statistically different from the postoperative ischaemic brain injury rate of 7/58 (12%, 4.9-21.3%; P=0.01) based on postoperative imaging. However, in a smaller group of participants with paired imaging (n=30), we did not identify the same effect (P=0.67). Patients with postoperative brain injury had elevated peak neurofilament light levels (median [inter-quartile range], 2.34 [2.24-2.64] log10 pg ml-1) compared with those without (1.86 [1.48-2.21] log10 pg ml-1; P=0.025). Delirium severity scores were higher in those with postoperative brain injury (19 [17-21]) compared with those without (7 [4-12]; P=0.01). CONCLUSION: Although limited by a small sample size, these data suggest that preoperative covert stroke occurs more commonly than previously anticipated. Plasma neurofilament light is a potential screening biomarker for postoperative ischaemic brain injury.

Association of delirium with increased short-term mortality among older emergency department patients: A cohort study.

STUDY OBJECTIVE: To evaluate the association between delirium and subsequent short-term mortality in geriatric patients presenting to the emergency department (ED). METHODS: This was an observational cohort study of adults age ≥75 years who presented to an academic ED and were screened for delirium during their ED visit. The Delirium Triage Screen followed by the Brief Confusion Assessment Method were used to ascertain the presence of delirium. In-hospital, 7-day, and 30-day mortality were compared between patients with and without ED delirium. Odds ratios with 95% confidence intervals (CIs) were calculated through logistic regression after adjusting for confounders including age, sex, history of dementia, ED disposition, and acuity. RESULTS: A total of 967 ED visits were included for analysis among which delirium was detected in 107 (11.1%). The median age of the cohort was 83 years (IQR 79, 88), 526 (54.4%) were female, 285 (29.5%) had documented dementia, and 171 (17.7%) had a high acuity Emergency Severity Index triage level 1 or 2. During the hospitalization, 5/107 (4.7%) of those with delirium and 4/860 (0.5%) of those without delirium died. Within 7 days of ED departure, 6/107 (5.6%) of those with delirium and 6/860 (0.7%) of those without delirium died (unadjusted OR 8.46, 95% CI 2.68-26.71). Within 30 days, 18/107 (16.8%) of those with delirium and 37/860 (4.3%) of those without delirium died (unadjusted OR 4.50, 95% CI 2.46-8.23). ED delirium remained associated with higher 7-day (adjusted OR 5.23, 95% CI 1.44-19.05, p = 0.008) and 30-day mortality (adjusted OR 2.82, 95% CI 1.45-5.46, p = 0.002). CONCLUSION: Delirium is an important prognostic factor that ED clinicians and nurses must be aware of to optimize delirium prevention, management, disposition, and communication with patients and families.

The Impact of Health Information Technology for Early Detection of Patient Deterioration on Mortality and Length of Stay in the Hospital Acute Care Setting: Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the impact of health information technology (HIT) for early detection of patient deterioration on patient mortality and length of stay (LOS) in acute care hospital settings. DATA SOURCES: We searched MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from 1990 to January 19, 2021. STUDY SELECTION: We included studies that enrolled patients hospitalized on the floor, in the ICU, or admitted through the emergency department. Eligible studies compared HIT for early detection of patient deterioration with usual care and reported at least one end point of interest: hospital or ICU LOS or mortality at any time point. DATA EXTRACTION: Study data were abstracted by two independent reviewers using a standardized data extraction form. DATA SYNTHESIS: Random-effects meta-analysis was used to pool data. Among the 30 eligible studies, seven were randomized controlled trials (RCTs) and 23 were pre-post studies. Compared with usual care, HIT for early detection of patient deterioration was not associated with a reduction in hospital mortality or LOS in the meta-analyses of RCTs. In the meta-analyses of pre-post studies, HIT interventions demonstrated a significant association with improved hospital mortality for the entire study cohort (odds ratio, 0.78 [95% CI, 0.70-0.87]) and reduced hospital LOS overall. CONCLUSIONS: HIT for early detection of patient deterioration in acute care settings was not significantly associated with improved mortality or LOS in the meta-analyses of RCTs. In the meta-analyses of pre-post studies, HIT was associated with improved hospital mortality and LOS; however, these results should be interpreted with caution. The differences in patient outcomes between the findings of the RCTs and pre-post studies may be secondary to confounding caused by unmeasured improvements in practice and workflow over time.

Major Surgery and Long Term Cognitive Outcomes: The Effect of Postoperative Delirium on Dementia in the Year Following Discharge.

BACKGROUND: Delirium is among the most common complications following major surgery. Delirium following medical illness is associated with the development of chronic cognitive decline. The objective of this study was to determine the association of postoperative delirium with dementia in the year following surgery. MATERIALS AND METHODS: This was a retrospective cohort study in a large health network (January 2013 to December 2019). All patients over age 50 undergoing surgery requiring an inpatient stay were included. Our main exposure was an episode of delirium. The primary outcome was a new dementia diagnosis in the 1 y following discharge. Secondary outcomes included hospital length of stay, non-home discharge destination, mortality and rehospitalizations in 1 y. RESULTS: There were 39,665 patients included, with a median age of 66. There were 4156 of 39,665 emergencies (10.5%). Specialties were general surgery (12,285/39,665, 31%) and orthopedics (11,503/39,665, 29%). There were 3327 (8.4%) patients with delirium. Delirious patients were older and were more likely to have comorbid conditions and undergone complex procedures. There were 1353 of 39,665 (3.5%) patients who developed dementia in the year following their surgery; 4930 of 39,665 (12.4%) who died; and 8200 of 39,665 (20.7%) who were readmitted. Delirium was associated with a new dementia diagnosis after adjusting for baseline characteristics (Odds ratio [OR] 13.9; 95% CI, 12.2-15.7). Similarly, delirium was also associated with 1 y mortality (OR 3.1; 95% CI 2.9-3.4) and readmission (OR 1.9, 95% CI 1.7-2.0). CONCLUSIONS: Postoperative delirium is the strongest factor associated with development of dementia in the year following a major operation. Strategies to prevent, identify, and treat delirium in the postoperative setting may improve long-term cognitive recovery.

Postoperative delirium and its relationship with biomarkers for dementia: a meta-analysis.

OBJECTIVES: This study seeks to identify Alzheimer's and related dementias (ADRD) biomarkers associated with postoperative delirium (POD) via meta-analysis. DESIGN: A comprehensive search was conducted. Studies met the following inclusion criteria: >18 years of age, identified POD with standardized assessment, and biomarker measured in the AT(N)-X (A = amyloid, T = tau, (N)=neurodegeneration, X-Other) framework. Exclusion criteria: focus on prediction of delirium, delirium superimposed on dementia, other neurologic or psychiatric disorders, or terminal delirium. Reviewers extracted and synthesized data for the meta-analysis. SETTING: Meta-analysis. PARTICIPANTS: Patients with POD. MEASUREMENTS: Primary outcome: association between POD and ATN-X biomarkers. Secondary outcomes involved sample heterogeneity. RESULTS: 28 studies were included in this meta-analysis. Studies focused on inflammatory and neuronal injury biomarkers; there were an insufficient number of studies for amyloid and tau biomarker analysis. Two inflammatory biomarkers (IL-6, and CRP) showed a significant relationship with POD (IL-6 n = 10, standardized mean difference (SMD): 0.53, 95% CI: 0.36-0.70; CRP n = 14, SMD: 0.53, 95% CI: 0.33-0.74). Two neuronal injury biomarkers (blood-based S100B and NfL) were positively associated with POD (S100B n = 5, SMD: 0.40, 95% CI: 0.11-0.69; NFL n = 2, SMD: 0.93, 95% CI: 0.28-1.57). Of note, many analyses were impacted by significant study heterogeneity. CONCLUSIONS: This meta-analysis identified an association between certain inflammatory and neuronal injury biomarkers and POD. Future studies will need to corroborate these relationships and include amyloid and tau biomarkers in order to better understand the relationship between POD and ADRD.

Association between emergency department modifiable risk factors and subsequent delirium among hospitalized older adults.

STUDY OBJECTIVE: To evaluate the association between potential emergency department (ED)-based modifiable risk factors and subsequent development of delirium among hospitalized older adults free of delirium at the time of ED stay. METHODS: Observational cohort study of patients aged ≥75 years who screened negative for delirium in the ED, were subsequently admitted to the hospital, and had delirium screening performed within 48 h of admission. Potential ED-based risk factors for delirium included ED length of stay (LOS), administration of opioids, benzodiazepines, antipsychotics, or anticholinergics, and the placement of urinary catheter while in the ED. Odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CIs) were calculated. RESULTS: Among 472 patients without delirium in the ED (mean age 84 years, 54.2% females), 33 (7.0%) patients developed delirium within 48 h of hospitalization. The ED LOS of those who developed delirium was similar to those who did not develop delirium (312.1 vs 325.6 min, MD -13.5 min, CI -56.1 to 29.0). Patients who received opioids in the ED were as likely to develop delirium as those who did not receive opioids (7.2% vs 6.9%: OR 1.04, CI 0.44 to 2.48). Patients who received benzodiazepines had a higher risk of incident delirium, the difference was clinically but not statistically significant (37.3% vs 6.5%, OR 5.35, CI 0.87 to 23.81). Intermittent urinary catheterization (OR 2.05, CI 1.00 to 4.22) and Foley placement (OR 3.69, CI 1.55 to 8.80) were associated with a higher risk of subsequent delirium. After adjusting for presence of dementia, only Foley placement in the ED remained significantly associated with development of in-hospital delirium (adjusted OR 3.16, CI 1.22 to 7.53). CONCLUSION: ED LOS and ED opioid use were not associated with higher risk of incident delirium in this cohort. Urinary catheterization in the ED was associated with an increased risk of subsequent delirium. These findings can be used to design ED-based initiatives and increase delirium prevention efforts.

Short-term Outcomes for Patients and Providers After Elective Tracheostomy in COVID-19-Positive Patients.

BACKGROUND: Urgent guidance is needed on the safety for providers of percutaneous tracheostomy in patients diagnosed with COVID-19. The objective of the study was to demonstrate that percutaneous dilational tracheostomy (PDT) with a period of apnea in patients requiring prolonged mechanical ventilation due to COVID-19 is safe and can be performed for the usual indications in the intensive care unit. METHODS: This study involves an observational case series at a single-center medical intensive care unit at a level-1 trauma center in patients diagnosed with COVID-19 who were assessed for tracheostomy. Success of a modified technique included direct visualization of tracheal access by bronchoscopy and a blind dilation and tracheostomy insertion during a period of patient apnea to reduce aerosolization. Secondary outcomes include transmission rate of COVID-19 to providers and patient complications. RESULTS: From April 6th, 2020 to July 21st, 2020, 2030 patients were admitted to the hospital with COVID-19, 615 required intensive care unit care (30.3%), and 254 patients required mechanical ventilation (12.5%). The mortality rate for patients requiring mechanical ventilation was 29%. Eighteen patients were assessed for PDT, and 11 (61%) underwent the procedure. The majority had failed extubation at least once (72.7%), and the median duration of intubation before tracheostomy was 15 d (interquartile range 13-24). The median positive end-expiratory pressure at time of tracheostomy was 10.8. The median partial pressure of oxygen (PaO2)/FiO2 ratio on the day of tracheostomy was 142.8 (interquartile range 104.5-224.4). Two patients had bleeding complications. At 1-week follow-up, eight patients still required ventilator support (73%). At the most recent follow-up, eight patients (73%) have been liberated from the ventilator, one patient (9%) died as a result of respiratory/multiorgan failure, and two were discharged on the ventilator (18%). Average follow-up was 20 d. None of the surgeons performing PDT have symptoms of or have tested positive for COVID-19. CONCLUSIONS: and relevance: PDT for patients with COVID-19 is safe for health care workers and patients despite higher positive end-expiratory pressure requirements and should be performed for the same indications as other causes of respiratory failure.

Postoperative delirium is associated with increased plasma neurofilament light.

While delirium is associated with cognitive decline and dementia, there is limited evidence to support causality for this relationship. Clarification of how delirium may cause cognitive decline, perhaps through evidence of contemporaneous neuronal injury, would enhance plausibility for a causal relationship. Dose-dependence of neuronal injury with delirium severity would further enhance the biological plausibility for this relationship. We tested whether delirium is associated with neuronal injury in 114 surgical patients recruited to a prospective biomarker cohort study. Patients underwent perioperative testing for changes in neurofilament light, a neuronal injury biomarker, as well as a panel of 10 cytokines, with contemporaneous assessment of delirium severity and incidence. A subset of patients underwent preoperative MRI. Initially we confirmed prior reports that neurofilament light levels correlated with markers of neurodegeneration [hippocampal volume (ΔR2 = 0.129, P = 0.015)] and white matter changes including fractional anisotropy of white matter (ΔR2 = 0.417, P < 0.001) with similar effects on mean, axial and radial diffusivity) in our cohort and that surgery was associated with increasing neurofilament light from preoperative levels [mean difference (95% confidence interval, CI) = 0.240 (0.178, 0.301) log10 (pg/ml), P < 0.001], suggesting putative neuronal injury. Next, we tested the relationship with delirium. Neurofilament light rose more sharply in participants with delirium compared to non-sufferers [mean difference (95% CI) = 0.251 (0.136, 0.367) log10 (pg/ml), P < 0.001]. This relationship showed dose-dependence, such that neurofilament light rose proportionately to delirium severity (ΔR2 = 0.199, P < 0.001). Given that inflammation is considered an important driver of postoperative delirium, next we tested whether neurofilament light, as a potential marker of neurotoxicity, may contribute to the pathogenesis of delirium independent of inflammation. From a panel of 10 cytokines, the pro-inflammatory cytokine IL-8 exhibited a strong correlation with delirium severity (ΔR2 = 0.208, P < 0.001). Therefore, we tested whether the change in neurofilament light contributed to delirium severity independent of IL-8. Neurofilament light was independently associated with delirium severity after adjusting for the change in inflammation (ΔR2 = 0.040, P = 0.038). These data suggest delirium is associated with exaggerated increases in neurofilament light and that this putative neurotoxicity may contribute to the pathogenesis of delirium itself, independent of changes in inflammation.

Relationships between preoperative cortical thickness, postoperative electroencephalogram slowing, and postoperative delirium.

BACKGROUND: It is unclear how preoperative neurodegeneration and postoperative changes in EEG delta power relate to postoperative delirium severity. We sought to understand the relative relationships between neurodegeneration and delta power as predictors of delirium severity. METHODS: We undertook a prospective cohort study of high-risk surgical patients (>65 yr old) to identify predictors of peak delirium severity (Delirium Rating Scale-98) with twice-daily delirium assessments (NCT03124303). Participants (n=86) underwent preoperative MRI; 54 had both an MRI and a postoperative EEG. Cortical thickness was calculated from the MRI and delta power from the EEG. RESULTS: In a linear regression model, the interaction between delirium status and preoperative mean cortical thickness (suggesting neurodegeneration) across the entire cortex was a significant predictor of delirium severity (P<0.001) when adjusting for age, sex, and performance on preoperative Trail Making Test B. Next, we included postoperative delta power and repeated the analysis (n=54). Again, the interaction between mean cortical thickness and delirium was associated with delirium severity (P=0.028), as was postoperative delta power (P<0.001). When analysed across the Desikan-Killiany-Tourville atlas, thickness in multiple individual cortical regions was also associated with delirium severity. CONCLUSIONS: Preoperative cortical thickness and postoperative EEG delta power are both associated with postoperative delirium severity. These findings might reflect different underlying processes or mechanisms. CLINICAL TRIAL REGISTRATION: NCT03124303.

Association between plasma tau and postoperative delirium incidence and severity: a prospective observational study.

BACKGROUND: Postoperative delirium is associated with increases in the neuronal injury biomarker, neurofilament light (NfL). Here we tested whether two other biomarkers, glial fibrillary acidic protein (GFAP) and tau, are associated with postoperative delirium. METHODS: A total of 114 surgical patients were recruited into two prospective biomarker cohort studies with assessment of delirium severity and incidence. Plasma samples were sent for biomarker analysis including tau, NfL, and GFAP, and a panel of 10 cytokines. We determined a priori to adjust for interleukin-8 (IL-8), a marker of inflammation, when assessing associations between biomarkers and delirium incidence and severity. RESULTS: GFAP concentrations showed no relationship to delirium. The change in tau from preoperative concentrations to postoperative Day 1 was greater in patients with postoperative delirium (P<0.001) and correlated with delirium severity (ρ=0.39, P<0.001). The change in tau correlated with increases in IL-8 (P<0.001) and IL-10 (P=0.0029). Linear regression showed that the relevant clinical predictors of tau changes were age (P=0.037), prior stroke/transient ischaemic attack (P=0.001), and surgical blood loss (P<0.001). After adjusting for age, sex, preoperative cognition, and change in IL-8, tau remained significantly associated with delirium severity (P=0.026). Using linear mixed effect models, only tau (not NfL or IL-8) predicted recovery from delirium (P<0.001). CONCLUSIONS: The change in plasma tau was associated with delirium incidence and severity, and resolved over time in parallel with delirium features. The impact of this putative perioperative neuronal injury biomarker on long-term cognition merits further investigation. CLINICAL TRIAL REGISTRATION: NCT02926417 and NCT03124303.

Delirium occurrence and association with outcomes in hospitalized COVID-19 patients.

Delirium is reported to be one of the manifestations of coronavirus infectious disease 2019 (COVID-19) infection. COVID-19 hospitalized patients are at a higher risk of delirium. Pathophysiology behind the association of delirium and COVID-19 is uncertain. We analyzed the association of delirium occurrence with outcomes in hospitalized COVID-19 patients, across all age groups, at Mayo Clinic hospitals.A retrospective study of all hospitalized COVID-19 patients at Mayo Clinic between March 1, 2020 and December 31, 2020 was performed. Occurrence of delirium and outcomes of mortality, length of stay, readmission, and 30-day mortality after hospital discharge were measured. Chi-square test, student t-test, survival analysis, and logistic regression analysis were performed to measure and compare outcomes of delirium group adjusted for age, sex, Charlson comorbidity score, and COVID-19 severity with no-delirium group.A total of 4351 COVID-19 patients were included in the study. Delirium occurrence in the overall study population was noted to be 22.4%. The highest occurrence of delirium was also noted in patients with critical COVID-19 illness severity. A statistically significant OR 4.35 (3.27-5.83) for in-hospital mortality and an OR 4.54 (3.25-6.38) for 30-day mortality after discharge in the delirium group were noted. Increased hospital length of stay, 30-day readmission, and need for skilled nursing facility on discharge were noted in the delirium group. Delirium in hospitalized COVID-19 patients is a marker for increased mortality and morbidity. In this group, outcomes appear to be much worse when patients are older and have a critical severity of COVID-19 illness.

Cohort study into the neural correlates of postoperative delirium: the role of connectivity and slow-wave activity.

BACKGROUND: Delirium frequently affects older patients, increasing morbidity and mortality; however, the pathogenesis is poorly understood. Herein, we tested the cognitive disintegration model, which proposes that a breakdown in frontoparietal connectivity, provoked by increased slow-wave activity (SWA), causes delirium. METHODS: We recruited 70 surgical patients to have preoperative and postoperative cognitive testing, EEG, blood biomarkers, and preoperative MRI. To provide evidence for causality, any putative mechanism had to differentiate on the diagnosis of delirium; change proportionally to delirium severity; and correlate with a known precipitant for delirium, inflammation. Analyses were adjusted for multiple corrections (MCs) where appropriate. RESULTS: In the preoperative period, subjects who subsequently incurred postoperative delirium had higher alpha power, increased alpha band connectivity (MC P<0.05), but impaired structural connectivity (increased radial diffusivity; MC P<0.05) on diffusion tensor imaging. These connectivity effects were correlated (r2=0.491; P=0.0012). Postoperatively, local SWA over frontal cortex was insufficient to cause delirium. Rather, delirium was associated with increased SWA involving occipitoparietal and frontal cortex, with an accompanying breakdown in functional connectivity. Changes in connectivity correlated with SWA (r2=0.257; P<0.0001), delirium severity rating (r2=0.195; P<0.001), interleukin 10 (r2=0.152; P=0.008), and monocyte chemoattractant protein 1 (r2=0.253; P<0.001). CONCLUSIONS: Whilst frontal SWA occurs in all postoperative patients, delirium results when SWA progresses to involve posterior brain regions, with an associated reduction in connectivity in most subjects. Modifying SWA and connectivity may offer a novel therapeutic approach for delirium. CLINICAL TRIAL REGISTRATION: NCT03124303, NCT02926417.

Predicting postoperative delirium severity in older adults: The role of surgical risk and executive function.

OBJECTIVES: Delirium is an important postoperative complication, yet predictive risk factors for postoperative delirium severity remain elusive. We hypothesized that the NSQIP risk calculation for serious complications (NSQIP-SC) or risk of death (NSQIP-D), and cognitive tests of executive function (Trail Making Tests A and B [TMTA and TMTB]), would be predictive of postoperative delirium severity. Further, we demonstrate how advanced statistical techniques can be used to identify candidate predictors. METHODS/DESIGN: Data from an ongoing perioperative prospective cohort study of 100 adults (65 y old or older) undergoing noncardiac surgery were analyzed. In addition to NSQIP-SC, NSQIP-D, TMTA, and TMTB, participant age, sex, American Society of Anesthesiologists (ASA) score, tobacco use, surgery type, depression, Framingham risk score, and preoperative blood pressure were collected. The Delirium Rating Scale-R-98 (DRS) measured delirium severity; the Confusion Assessment Method (CAM) identified delirium. LASSO and best subsets linear regression were employed to identify predictive risk factors. RESULTS: Ninety-seven participants with a mean age of 71.68 ± 4.55, 55% male (31/97 CAM+, 32%), and a mean peak DRS of 21.5 ± 6.40 were analyzed. LASSO and best subsets regression identified NSQIP-SC and TMTB to predict postoperative delirium severity (P < 00.001, adjusted R2 : 0.30). NSQIP-SC and TMTB were also selected as predictors for postoperative delirium incidence (AUROC 0.81, 95% CI, 0.72-0.90). CONCLUSIONS: In this cohort, we identified NSQIP risk score for serious complications and a measure of executive function, TMT-B, to predict postoperative delirium severity using advanced modeling techniques. Future studies should investigate the utility of these variables in a formal delirium severity prediction model.

Increasing Hospital at Home Enrollment Through Decentralization With Agile Science.

LEVEL OF EVIDENCE: 4, Descriptive quality improvement project.