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Item Aging and Post-Intensive Care Syndrome–Family (PICS-F): A Critical Need for Geriatric Psychiatry(Elsevier, 2019) Serrano, Patricia; Kheir, You Na P.; Wang, Sophia; Khan, Sikandar; Scheunemann, Leslie; Khan, Babar; Psychiatry, School of MedicinePost-intensive care syndrome–family (PICS-F) describes the psychological symptoms that affect the family members of patients hospitalized in the intensive care unit (ICU) or recently discharged from the ICU. Geriatric psychiatrists should be concerned about PICS-F for several reasons. First, ICU hospitalization in older adults is associated with higher rates of cognitive and physical impairment, compared to older adults hospitalized in non-ICU settings or dwelling in the community. This confers a special burden on the caregivers of these older ICU survivors compared to other geriatric populations. Second, as caregivers themselves age, caring for this unique burden can be more challenging compared to other geriatric populations. Third, evidence for models of care centered on patients with multimorbidity and their caregivers is limited. A deeper understanding of how to care for PICS and PICS-F may inform clinical practice for other geriatric populations with multimorbidity and their caregivers. Geriatric psychiatrists may play a key role in delivering coordinated care for PICS-F by facilitating timely diagnosis and interdisciplinary collaboration, advocating for the healthcare needs of family members suffering from PICS-F, and leading efforts within healthcare systems to increase awareness and treatment of PICS-F. This clinical review will appraise the current literature about the impact of critical illness on the family members of ICU survivors and identify crucial gaps in our knowledge about PICS-F among aging patients and caregivers.Item Association between Change in the peripheral biomarkers of inflammation, astrocyte activation, and neuroprotection at one week of critical illness and hospital mortality in patients with delirium: A prospective cohort study(Public Library of Science, 2023-09-01) Khan, Sikandar H.; Perkins, Anthony J.; Eltarras, Ahmed M.; Chi, Rosalyn; Athar, Ammar A.; Wang, Sophia; Campbell, Noll L.; Gao, Sujuan; Boustani, Malaz A.; Khan, Babar A.; Medicine, School of MedicineObjective: In critically ill adults with delirium, biomarkers of systemic inflammation, astrocyte activation, neuroprotection, and systemic inflammation measured at one week of critical illness may be associated with mortality. Design: Prospective observational study. Setting: Intensive care unit (ICU). Patients: 178 ICU patients with delirium, alive and remaining in ICU at one week. Interventions: None. Measurements and main results: Blood samples collected for a pair of previously published, negative, clinical trials were utilized. Samples were collected at study enrollment/ICU admission (Day 1 sample) and one week later (Day 8 sample), and analyzed for interleukins (IL)-6, 8, 10, Insulin-like Growth Factor (IGF), S100 Binding Protein (S100B), Tumor Necrosis Factor Alpha (TNF-A) and C-Reactive Protein (CRP). Delirium, delirium severity, and coma were assessed twice daily using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), CAM-ICU-7, and Richmond Agitation-Sedation Scale (RASS), respectively. Mortality was assessed until discharge using the electronic medical record. Logistic regression models adjusting for age, sex, severity of illness, comorbidities, sepsis, and randomization status, were used to assess the relationship among biomarkers and mortality. Higher IL-10 quartiles at day 8 were associated with increased odds of hospital mortality (IL-10: OR 2.00 95%CI: 1.1-3.65, p = 0.023). There was a significant interaction between day 1 and day 8 biomarker quartiles only for IL-6. Patients with IL-6 values in the first three quartiles on admission to the ICU that transitioned to higher IL-6 quartiles at day 8 had increased probability of hospital mortality. Conclusion: In this hypothesis-generating study, higher IL-6 and IL-10 quartiles at one week, and increase in IL-6 from day 1 to day 8 were associated with increased hospital mortality. Studies with larger sample sizes are needed to confirm the mechanisms for these observations.Item Association between plasma tau and postoperative delirium incidence and severity: a prospective observational study(Elsevier, 2021) Ballweg, Tyler; White, Marissa; Parker, Margaret; Casey, Cameron; Bo, Amber; Farahbakhsh, Zahra; Kayser, Austin; Blair, Alexander; Lindroth, Heidi; Pearce, Robert A.; Blennow, Kaj; Zetterberg, Henrik; Lennertz, Richard; Sanders, Robert D.; Medicine, School of MedicineBackground: 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.Item Biomarkers of Delirium Duration and Delirium Severity in the ICU(Wolters Kluwer, 2020-03) Khan, Babar A.; Perkins, Anthony J.; Prasad, Nagendra K.; Shekhar, Anantha; Campbell, Noll L.; Gao, Sujuan; Wang, Sophia; Khan, Sikandar H.; Marcantonio, Edward R.; Twigg, Homer L., III.; Boustani, Malaz A.; Medicine, School of MedicineObjectives: Both delirium duration and delirium severity are associated with adverse patient outcomes. Serum biomarkers associated with delirium duration and delirium severity in ICU patients have not been reliably identified. We conducted our study to identify peripheral biomarkers representing systemic inflammation, impaired neuroprotection, and astrocyte activation associated with delirium duration, delirium severity, and in-hospital mortality. Design: Observational study. Setting: Three Indianapolis hospitals. Patients: Three-hundred twenty-one critically ill delirious patients. Interventions: None. Measurements and main results: We analyzed the associations between biomarkers collected at delirium onset and delirium-/coma-free days assessed through Richmond Agitation-Sedation Scale/Confusion Assessment Method for the ICU, delirium severity assessed through Confusion Assessment Method for the ICU-7, and in-hospital mortality. After adjusting for age, gender, Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity score, sepsis diagnosis and study intervention group, interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100β levels in quartile 4 were negatively associated with delirium-/coma-free days by 1 week and 30 days post enrollment. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium-/coma-free days at both time points. Interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100β levels in quartile 4 were also associated with delirium severity by 1 week. At hospital discharge, interleukin-6, -8, and -10 retained the association but tumor necrosis factor-α, C-reactive protein, and S-100β lost their associations with delirium severity. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium severity at both time points. Interleukin-8 and S-100β levels in quartile 4 were also associated with higher in-hospital mortality. Interleukin-6 and -10, tumor necrosis factor-α, and insulin-like growth factor-1 were not found to be associated with in-hospital mortality. Conclusions: Biomarkers of systemic inflammation and those for astrocyte and glial activation were associated with longer delirium duration, higher delirium severity, and in-hospital mortality. Utility of these biomarkers early in delirium onset to identify patients at a higher risk of severe and prolonged delirium, and delirium related complications during hospitalization needs to be explored in future studies.Item Biomarkers of Delirium Duration and Delirium Severity: A Reply(Wolters Kluwer, 2021) Khan, Sikandar H.; Perkins, Anthony J.; Gao, Sujuan; Khan, Babar A.; Medicine, School of MedicineItem The CAM-ICU-7 Delirium Severity Scale: A Novel Delirium Severity Instrument for Use in the Intensive Care Unit(Wolters Kluwer, 2017-05) Khan, Babar A.; Perkins, Anthony J.; Gao, Sujuan; Hui, Siu L.; Campbell, Noll L.; Farber, Mark O.; Chlan, Linda L.; Boustani, Malaz A.; Medicine, School of MedicineOBJECTIVES: Delirium severity is independently associated with longer hospital stays, nursing home placement, and death in patients outside the ICU. Delirium severity in the ICU is not routinely measured because the available instruments are difficult to complete in critically ill patients. We designed our study to assess the reliability and validity of a new ICU delirium severity tool, the Confusion Assessment Method for the ICU-7 delirium severity scale. DESIGN: Observational cohort study. SETTING: Medical, surgical, and progressive ICUs of three academic hospitals. PATIENTS: Five hundred eighteen adult (≥ 18 yr) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients received the Confusion Assessment Method for the ICU, Richmond Agitation-Sedation Scale, and Delirium Rating Scale-Revised-98 assessments. A 7-point scale (0-7) was derived from responses to the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale items. Confusion Assessment Method for the ICU-7 showed high internal consistency (Cronbach's α = 0.85) and good correlation with Delirium Rating Scale-Revised-98 scores (correlation coefficient = 0.64). Known-groups validity was supported by the separation of mechanically ventilated and nonventilated assessments. Median Confusion Assessment Method for the ICU-7 scores demonstrated good predictive validity with higher odds (odds ratio = 1.47; 95% CI = 1.30-1.66) of in-hospital mortality and lower odds (odds ratio = 0.8; 95% CI = 0.72-0.9) of being discharged home after adjusting for age, race, gender, severity of illness, and chronic comorbidities. Higher Confusion Assessment Method for the ICU-7 scores were also associated with increased length of ICU stay (p = 0.001). CONCLUSIONS: Our results suggest that Confusion Assessment Method for the ICU-7 is a valid and reliable delirium severity measure among ICU patients. Further research comparing it to other delirium severity measures, its use in delirium efficacy trials, and real-life implementation is needed to determine its role in research and clinical practice.Item Clinician and Visitor Activity Patterns in an Intensive Care Unit Room: A Study to Examine How Ambient Monitoring Can Inform the Measurement of Delirium Severity and Escalation of Care(MDPI, 2024-10-14) Nalaie, Keivan; Herasevich, Vitaly; Heier, Laura M.; Pickering, Brian W.; Diedrich, Daniel; Lindroth, Heidi; Center for Health Innovation and Implementation Science, School of MedicineThe early detection of the acute deterioration of escalating illness severity is crucial for effective patient management and can significantly impact patient outcomes. Ambient sensing technology, such as computer vision, may provide real-time information that could impact early recognition and response. This study aimed to develop a computer vision model to quantify the number and type (clinician vs. visitor) of people in an intensive care unit (ICU) room, study the trajectory of their movement, and preliminarily explore its relationship with delirium as a marker of illness severity. To quantify the number of people present, we implemented a counting-by-detection supervised strategy using images from ICU rooms. This was accomplished through developing three methods: single-frame, multi-frame, and tracking-to-count. We then explored how the type of person and distribution in the room corresponded to the presence of delirium. Our designed pipeline was tested with a different set of detection models. We report model performance statistics and preliminary insights into the relationship between the number and type of persons in the ICU room and delirium. We evaluated our method and compared it with other approaches, including density estimation, counting by detection, regression methods, and their adaptability to ICU environments.Item Cohort study into the neural correlates of postoperative delirium: the role of connectivity and slow-wave activity(Elsevier, 2020-07) Tanabe, Sean; Mohanty, Rosaleena; Lindroth, Heidi; Casey, Cameron; Ballweg, Tyler; Farahbakhsh, Zahra; Krause, Bryan; Prabhakaran, Vivek; Banks, Matthew I.; Sanders, Robert D.; Medicine, School of MedicineBackground: 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.Item Comparative Implementation of a Brief App-Directed Protocol for Delirium Identification by Hospitalists, Nurses, and Nursing Assistants : A Cohort Study(American College of Physicians, 2022) Marcantonio, Edward R.; Fick, Donna M.; Jung, Yoojin; Inouye, Sharon K.; Boltz, Marie; Leslie, Douglas L.; Husser, Erica K.; Shrestha, Priyanka; Moore, Amber; Sulmonte, Kimberlyann; Siuta, Jonathan; Boustani, Malaz; Ngo, Long H.; Medicine, School of MedicineBackground: Systematic screening improves delirium identification among hospitalized older adults. Little data exist on how to implement such screening. Objective: To test implementation of a brief app-directed protocol for delirium identification by physicians, nurses, and certified nursing assistants (CNAs) in real-world practice relative to a research reference standard delirium assessment (RSDA). Design: Prospective cohort study. Setting: Large urban academic medical center and small rural community hospital. Participants: 527 general medicine inpatients (mean age, 80 years; 35% with preexisting dementia) and 399 clinicians (53 hospitalists, 236 nurses, and 110 CNAs). Measurements: On 2 study days, enrolled patients had an RSDA. Subsequently, CNAs performed an ultra-brief 2-item screen (UB-2) for delirium, whereas physicians and nurses performed a 2-step protocol consisting of the UB-2 followed in those with a positive screen result by the 3-Minute Diagnostic Assessment for the Confusion Assessment Method. Results: Delirium was diagnosed in 154 of 924 RSDAs (17%) and in 114 of 527 patients (22%). The completion rate for clinician protocols exceeded 97%. The CNAs administered the UB-2 in a mean of 62 seconds (SD, 51). The 2-step protocols were administered in means of 104 seconds (SD, 99) by nurses and 106 seconds (SD, 105) by physicians. The UB-2 had sensitivities of 88% (95% CI, 72% to 96%), 87% (CI, 73% to 95%), and 82% (CI, 65% to 91%) when administered by CNAs, nurses, and physicians, respectively, with specificities of 64% to 70%. The 2-step protocol had overall accuracy of 89% (CI, 83% to 93%) and 87% (CI, 81% to 91%), with sensitivities of 65% (CI, 48% to 79%) and 63% (CI, 46% to 77%) and specificities of 93% (CI, 88% to 96%) and 91% (CI, 86% to 95%), for nurses and physicians, respectively. Two-step protocol sensitivity for moderate to severe delirium was 78% (CI, 54% to 91%). Limitation: Two sites; limited diversity. Conclusion: An app-directed protocol for delirium identification was feasible, brief, and accurate, and CNAs and nurses performed as well as hospitalists.Item Comparative Salary-Related Costs of a Brief App-directed Delirium Identification Protocol by Hospitalists, Nurses, and Nursing Assistants(Wiley, 2022) Leslie, Douglas L.; Fick, Donna M.; Moore, Amber; Inouye, Sharon K.; Jung, Yoojin; Ngo, Long H.; Boltz, Marie; Husser, Erica; Shrestha, Priyanka; Boustani, Malaz; Marcantonio, Edward R.; Medicine, School of MedicineBackground: Systematic screening can improve delirium identification among hospitalized older adults. Prior studies have shown clinicians and health system leaders may believe they do not have the time and resources for assessment. We conducted a comparative salary-related cost analysis of an adaptive delirium identification protocol directed by an iPad app. Methods: We recruited 527 older adult medicine patients from an urban academic medical center (n = 269) and a rural community hospital (n = 258). Physicians and nurses completed the two-step Ultra-brief Confusion Assessment Method (UB-CAM) protocol (with or without a skip pattern), while certified nursing assistants completed only the UB-2 ultra-brief screen. The sample included 527 patients (average age 80, 57% women, 35% with dementia). Time required to administer the protocol was collected automatically by the iPad app. Salary-related costs of screening were determined by multiplying the time required by the hourly wage for the three disciplines, as obtained from national and regional published healthcare salary cost data. Cost estimates for entire hospital implementation were also calculated. Results: Participants were screened on 924 hospital days by 399 clinicians (53 physicians, 236 nurses, 110 CNAs). For the UB-2, CNAs cost per screen was lower than the other clinician types ($0.37 per screen vs. $0.73 for nurses and $2.39 for hospitalists). For the UB-CAM with skip (UB-CAM), costs per protocol were $1.10 for nurses vs. $3.61 for physicians. The annual salary-related costs of hospital-wide implementation of a nurse-based UB-CAM protocol in a medium-sized (300-bed) hospital was $63,015 plus $4356 for initial and annual training. Conclusions: CNAs and nurses had the lowest salary-associated costs for app-directed CAM-based delirium screening and identification, respectively. Salary-related annual hospital costs for the most efficient protocols in a medium-sized hospital were less than the annual cost of hiring 1 FTE of the discipline performing the protocols.