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Hertrich AC, Grundei S. [Delirium: long-term sequelae and aftercare with special consideration to posttraumatic stress disorder]. Med Klin Intensivmed Notfmed 2025; 120:397-402. [PMID: 40323391 DOI: 10.1007/s00063-025-01279-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 03/11/2025] [Accepted: 04/01/2025] [Indexed: 05/27/2025]
Abstract
Delirium is a frequent syndrome among hospitalized patients, with a prevalence of 10-30% on general wards, up to 50% on palliative care units and 30-80% on intensive care units (ICU). Defined in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) as an acute, reversible disturbance of attention, cognition and consciousness, delirium is associated with infections, surgery, trauma and other disease conditions. Risk factors include advanced age, pre-existing neurocognitive disorders and substance abuse. Delirium is associated with increased mortality, longer hospitalization and the occurrence of post-hospital discharge complications, including post-intensive care syndrome (PICS) and posttraumatic stress disorder (PTSD). A structured post-inpatient management is limited, highlighting the need for specialized aftercare clinics. On the ICU early detection through tools, such as confusion assessment method for the ICU (CAM-ICU) and preventive measures, including the ABCDEF bundle, are essential. Family involvement and patient education can mitigate long-term effects. A greater awareness of the impact of delirium and the long-term sequelae is crucial to improve patient recovery and to address both physical and psychological needs.
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Affiliation(s)
- Anna Carola Hertrich
- Klinik für Intensivmedizin, Universitätsklinikum Hamburg-Eppendorf, Zentrum für Anästhesiologie und Intensivmedizin, Martinistraße 52, 20246, Hamburg, Deutschland.
| | - Sophia Grundei
- Abteilung für Innere Medizin I, Medizinische Universität Innsbruck, Gemeinsame Einrichtung für Internistische Intensiv- und Notfallmedizin, Anichstraße 35, 6020, Innsbruck, Österreich.
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Rivera C, Kunkel D, Her M, Qureshi S, Pearce RA, Sanders RD, Lennertz R. The 3-Minute Diagnostic Confusion Assessment Method severity score correlates with the Delirium Rating Scale-Revised-98 and with biomarkers of delirium. BJA OPEN 2025; 14:100398. [PMID: 40331035 PMCID: PMC12051057 DOI: 10.1016/j.bjao.2025.100398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 03/17/2025] [Indexed: 05/08/2025]
Abstract
Background Several methods are used to measure delirium severity in the postoperative period. Here, we compare severity scores from two common assessment methods: the 3-Minute Diagnostic Confusion Assessment Method (3D-CAM) and the Delirium Rating Scale-Revised-98 (DRS). Methods Data were collected as part of an ongoing observational cohort study of perioperative delirium in patients >65 yr old undergoing major elective surgery with an anticipated hospital stay of at least 2 days. Patients were excluded if they had a documented history of dementia, resided in a nursing home, underwent neurosurgery, or could not complete neurocognitive testing. Patients underwent paired 3D-CAM and DRS assessments before and after operation along with EEG, cognitive testing, and plasma biomarker analysis. Results Of 226 subjects enrolled, 204 completed both the 3D-CAM and DRS assessments. Peak 3D-CAM severity (3D-CAM-S) scores correlated with peak DRS severity scores, for both the raw (ρ=0.74, P<0.001) and short form method (ρ=0.66, P<0.001). Peak 3D-CAM-S raw scores also correlated with delirium duration and severity duration area under the curve measures (ρ=0.71, P<0.001 and ρ=0.91, P<0.001, respectively). Similar to prior reports with the DRS, 3D-CAM-S raw scores correlated with worse performance on the Trail Making Test B (ρ=0.37, P<0.001, n=177), slow-wave electroencephalogram power (ρ=0.3, P=0.001, n=73), and plasma neurofilament light (ρ=0.26, P<0.05, n=61) and tau (ρ=0.41, P<0.001, n=63). Conclusions The 3D-CAM-S severity scores correlated with DRS, delirium duration, and biomarkers of delirium. The 3D-CAM, which is easier to implement than the DRS in postoperative patients, may provide a comparable assessment of delirium severity in this population. Clinical trial registration NCT03124303.
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Affiliation(s)
- Cameron Rivera
- Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - David Kunkel
- Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Maihlee Her
- Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Simran Qureshi
- Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Robert A. Pearce
- Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Robert D. Sanders
- University of Sydney, Sydney, NSW, Australia
- Department of Anaesthetics, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Richard Lennertz
- Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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Zhu S, Ding X, Bo J, Xia T, Gu X. Novel drug targets for delirium based on genetic causality. J Affect Disord 2025; 378:128-137. [PMID: 40023257 DOI: 10.1016/j.jad.2025.02.095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 02/24/2025] [Accepted: 02/25/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND Effective treatment and prevention of delirium remain challenging, largely due to the limited efficiency in identifying and validating drug targets. To address this gap, we performed a systematic Mendelian Randomization (MR) study of the druggable genome to identify potential therapeutic targets for delirium. METHODS To identify therapeutic targets for delirium, we conducted MR and colocalization analyses using cis-eQTL data (31,684 blood samples and 1387 brain samples) and genome-wide association study (GWAS) data for delirium (discovery cohort N = 431,880; validation cohort N = 403,037). This approach enabled us to identify annotated druggable gene targets with significant associations with delirium. Additional analyses included phenome-wide association studies (PheWAS), enrichment analyses, protein network construction, drug prediction, molecular docking, and mediation analyses to assess the therapeutic and clinical relevance of these targets. RESULTS Five genes were identified as significant therapeutic targets for delirium: C4BPA, A2M, GRIK4, and C1R from blood samples, and SUMF1 from both blood and brain tissues. These genes are biologically significant for their strong association with immune function. At the gene level, PheWAS identified associations between C4BPA and other traits. Molecular docking demonstrated strong binding between drugs and proteins with available structural data. Mediation analysis revealed that C4BPA explained 16.7 % of the aging-related risk for delirium. CONCLUSION Our MR analysis identifies 5 potential druggable targets for the treatment of delirium. Drugs targeting these genes are more likely to succeed in clinical trials and are expected to prioritize the development of delirium treatments while reducing drug development costs.
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Affiliation(s)
- Shouqiang Zhu
- Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Medical School, Nanjing University, Nanjing, Jiangsu Province, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu Province, China
| | - Xiahao Ding
- Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Medical School, Nanjing University, Nanjing, Jiangsu Province, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu Province, China
| | - Jinhua Bo
- Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China
| | - Tianjiao Xia
- Medical School, Nanjing University, Nanjing, Jiangsu Province, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
| | - Xiaoping Gu
- Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
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Schöler LM, Graf L, Airola A, Ritzi A, Simon M, Peltonen LM. Determining the ground truth for the prediction of delirium in adult patients in acute care: a scoping review. JAMIA Open 2025; 8:ooaf037. [PMID: 40421319 PMCID: PMC12105575 DOI: 10.1093/jamiaopen/ooaf037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 04/10/2025] [Accepted: 04/25/2025] [Indexed: 05/28/2025] Open
Abstract
Objective Delirium is a severe condition, often underreported and linked to adverse outcomes such as increased mortality and prolonged hospitalization. Despite its significance, delirium prediction is often hindered by underreporting and inconsistent labeling, highlighting the need for models trained on reliably labeled data (ground truth). This review examines (i) practices for determining labels in delirium prediction models and (ii) how study designs affect label quality, aiming to identify key considerations for improving model reliability. Materials and Methods A search of Cochrane, PubMed, and IEEE identified 120 studies that met the inclusion criteria. Results To establish the ground truth, 40.8% of studies used routine data, while 42.5% used primary data. The Confusion Assessment Method (CAM) was the most widely used assessment tool (60. 0%). Label and data leakage occurred in 35.0% of studies. High Risk of Bias (RoB) was a recurring issue, with 31.7% of studies lacking sufficient reporting and 36.7% showing inadequate outcome determination. Studies using primary data had lower RoB, whereas those with unclear label sources displayed higher RoB. Discussion Our findings underscore the importance of careful planning in determining the ground truth frequently neglected in existing studies. To address these challenges, we provide a decision support flowchart to guide the development of more accurate and reliable prediction models. Conclusion This review uncovers significant variability in labeling methods and discusses how this may affect delirium prediction model reliability. Highlighting the importance of addressing underreporting bias and providing guidance for developing more robust models.
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Affiliation(s)
- Lili M Schöler
- Department of Nursing, Medical Center—University of Freiburg, Freiburg 79106, Germany
- Department of Nursing Science, University of Turku, Turku 20520, Finland
| | - Lisa Graf
- Department of Neurology, Medical Center—University of Freiburg, Freiburg 79106, Germany
- Neurorobotics Lab, Department of Computer Science, University of Freiburg, Freiburg 79110, Germany
| | - Antti Airola
- Department of Computing, University of Turku, Turku 20500, Finland
| | - Alexander Ritzi
- Department of Nursing, Medical Center—University of Freiburg, Freiburg 79106, Germany
- Centre for Geriatric Medicine and Gerontology (ZGGF), Medical Center—University of Freiburg, Freiburg 79106, Germany
| | - Michael Simon
- Institute of Nursing Science, Department of Public Health, University of Basel, Basel 4056, Switzerland
| | - Laura-Maria Peltonen
- Department of Nursing Science, University of Turku, Turku 20520, Finland
- Research Services, The Wellbeing Services County of Southwest Finland, Turku 20521, Finland
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King S, Uleberg O, Pedersen SA, Bjørnsen LP. Outcomes associated with older patients who present or develop delirium in the emergency department: protocol for a systematic review and meta-analysis. BMJ Open 2025; 15:e095495. [PMID: 40379347 PMCID: PMC12086875 DOI: 10.1136/bmjopen-2024-095495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 04/28/2025] [Indexed: 05/19/2025] Open
Abstract
INTRODUCTION Delirium is commonly observed in older patients who are admitted to the emergency department (ED). Previous systematic reviews have identified poor outcomes associated with delirium in surgical, intensive care and other hospital settings, yet none have specifically considered the ED. This systematic review aims to examine associations between older patients who present or develop delirium in the ED and adverse outcomes within the hospital and after discharge. METHODS AND ANALYSIS Searches will be conducted in MEDLINE, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library. There will be no date or language restrictions. Key terms will include concepts related to delirium, the ED and older adults. Observational studies or non-intervention clinical studies will be included that compare outcomes in older patients (ie, ≥65 years) with and without delirium. Outcomes of interest will include length of hospital stay, non-home discharge (eg, nursing home/residential aged care facility), cognitive impairment, decreased physical function, mortality, readmission to hospital and quality of life measures. Two reviewers will independently screen the studies. Data extraction and quality assessment will be extracted by one reviewer and checked by a second reviewer, with any disagreements resolved by discussion or by a third reviewer. Where appropriate, data will be combined in a meta-analysis and a GRADE assessment will be made for each outcome. All methods will be guided by the Cochrane Handbook and the Centre for Reviews and Dissemination and reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis statement as well as the recommendations set out by the Meta-analysis Of Observational Studies in Epidemiology group. ETHICS AND DISSEMINATION As this systematic review will use published data, ethical approval is not required. The results will be disseminated through a peer-reviewed publication and conference presentations. PROSPERO REGISTRATION NUMBER CRD42024594975.
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Affiliation(s)
- Sarah King
- Trondheim Emergency Department Research Group (TEDRG), Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Oddvar Uleberg
- Trondheim Emergency Department Research Group (TEDRG), Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Research and Development, Norwegian Air Ambulance Foundation, Oslo, Norway
- Department of Emergency Medicine and Pre-Hospital Services, St. Olav's Hospital, Trondheim, Norway
| | - Sindre A Pedersen
- The Medicine and Health Library, Library Section for Research Support, Data and Analysis, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Lars Petter Bjørnsen
- Trondheim Emergency Department Research Group (TEDRG), Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Emergency Medicine and Pre-Hospital Services, St. Olav's Hospital, Trondheim, Norway
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Li A, Song Y, Shi W, Mi W, Lou J, Liu J. Association between combinations of preoperative comorbidities and postoperative delirium in older patients: a matched cohort study. BMC Anesthesiol 2025; 25:245. [PMID: 40375126 DOI: 10.1186/s12871-025-03110-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 05/02/2025] [Indexed: 05/18/2025] Open
Abstract
BACKGROUND The current study aimed to investigate which one or certain combinations of preoperative comorbidities were associated with higher risk of postoperative delirium. METHODS This propensity-score-matched cohort study analyzed a retrospective dataset of elderly patients undergoing surgery at the First Medical Center of the Chinese PLA General Hospital from January 2014 to April 2019. Univariate risk factors were selected by logistic regression, and then the combinations of these univariate factors were compared. RESULTS We identified 1034 older patients developed postoperative delirium (POD) within seven days after surgery, and 3102 patients without POD were matched by propensity score matching analysis at a ratio of 1:3 for those with POD. Eight preoperative comorbidities, including hypertension, diabetes, atrial fibrillation, cerebrovascular disease, Parkinson's disease, epilepsy, depression, and chronic obstructive pulmonary disease (COPD) were more common in patients diagnosed with POD after surgery than those without POD. Patients with POD were more likely to concurrently suffer from the combinations of hypertension and cerebrovascular disease, or hypertension and COPD. CONCLUSIONS Several preoperative comorbidities are associated with a higher risk of POD in older surgical patient. Those suffering from combinations of preoperative comorbidities were more likely to develop POD, and hypertension plays a central role in these combinations.
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Affiliation(s)
- Ao Li
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yuxiang Song
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Wenzhu Shi
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Weidong Mi
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
- National Clinical Research Center for Geriatric Diseases, Beijing, China.
| | - Jingsheng Lou
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
- National Clinical Research Center for Geriatric Diseases, Beijing, China.
| | - Jing Liu
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
- National Clinical Research Center for Geriatric Diseases, Beijing, China.
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Benn L, Shah N, McKinney A, Min L, Aleem I, Luzum M, Vlisides PE. Delirium screening and alerting systems for older hospital inpatients. BMC Health Serv Res 2025; 25:655. [PMID: 40336091 PMCID: PMC12060402 DOI: 10.1186/s12913-025-12829-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Accepted: 04/30/2025] [Indexed: 05/09/2025] Open
Abstract
BACKGROUND Delirium often goes unrecognized in the hospital, leading to missed opportunities for management. The objective of this study was to test a multicomponent program for delirium screening and reporting for older, hospitalized adults. METHODS We implemented a multicomponent delirium screening and alerting program within two university hospital units for all patients ≥ 70 years of age. The initiative compared performance of the 4 'A's Test, Nursing Delirium Screening Scale, and Confusion Assessment Method. Additionally, the study team provided recurrent educational sessions with nurses and implemented pager and electronic health record alerts for patients who screened positive for delirium. Nurses were then surveyed about their perspectives, and clinical outcomes were abstracted from the medical record. RESULTS Compared to the Confusion Assessment Method, the proportion of positive screens was significantly higher (positive screens/admissions) with the 4 'A's Test (49/448, 11% vs. 12/399, 3%, p < 0.001) and the Nursing Delirium Screening Scale (83/539, 15% vs. 12/399, 3%, p < 0.001). Among surveyed nurses, 32/41 (78%) expressed that the alerting system provided at least "moderate" motivation to screen for delirium, and 35/41 (85%) voiced that it provided at least "moderate" motivation to record positive screens. Most respondents (23/42, 55%) reported recurrent educational sessions as "very helpful." Positive screens were associated with higher mortality (6.6% vs. 1.9%, p = 0.003), longer hospitalizations (13 [± 11] days vs. 7 [± 11], p < 0.001), and higher likelihood of discharge to care facilities (45% vs. 23%, p < 0.001). CONCLUSIONS Positive delirium screening rates were higher with the 4AT and NuDesc compared to the CAM. Additionally, alerting systems and educational initiatives served as motivating factors for delirium screening and charting.
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Affiliation(s)
- Lakeshia Benn
- Department of Inpatient Rehabilitation, Michigan Medicine, Ann Arbor, MI, USA
- College of Health Professions & McAuley School of Nursing, University of Detroit Mercy, Detroit, MI, USA
| | - Nirav Shah
- Department of Anesthesiology, University of Michigan Medical School, 1H247 UH, SPC-5048, 1500 East Medical Center Drive, MI, 48109-5048, Ann Arbor, USA
| | - Amy McKinney
- Department of Anesthesiology, University of Michigan Medical School, 1H247 UH, SPC-5048, 1500 East Medical Center Drive, MI, 48109-5048, Ann Arbor, USA
| | - Lillian Min
- Department of Internal Medicine, Division of Geriatric & Palliative Medicine, Michigan Medicine, Ann Arbor, MI, USA
- VA Ann Arbor Healthcare System, Department of Internal Medicine, Division of Geriatric Research, Education, and Clinical Center (GRECC), Ann Arbor, MI, USA
| | - Ilyas Aleem
- Department of Orthopaedic Surgery, Michigan Medicine, Ann Arbor, MI, USA
| | - Matthew Luzum
- Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI, USA
| | - Phillip E Vlisides
- Department of Anesthesiology, University of Michigan Medical School, 1H247 UH, SPC-5048, 1500 East Medical Center Drive, MI, 48109-5048, Ann Arbor, USA.
- Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI, USA.
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Lu Z, Wang X, Mao T, Liu L, Zhang J. Evidence from a Mendelian randomization study: Delirium's noncausal role in dementia onset. Neuroscience 2025; 573:247-253. [PMID: 40132793 DOI: 10.1016/j.neuroscience.2025.03.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 03/06/2025] [Accepted: 03/13/2025] [Indexed: 03/27/2025]
Abstract
BACKGROUND Previous observational studies have suggested a possible association between dementia and delirium. However, these findings might be influenced by confounding variables. Thus, our study aimed to investigate the causal relationship between dementia and delirium using a bidirectional Mendelian randomization (MR) analysis. METHODS In our investigation, bidirectional MR analysis was conducted by summary statistics from genome-wide association studies (GWAS). This enabled us to evaluate the causal impact of delirium and different types of dementia, such as Alzheimer's dementia (AD), vascular dementia (VaD) and Lewy body dementia (LD). RESULTS According to MR analysis, there was a significant positive correlation between delirium risk and AD (odds ratio [OR] = 1.363; 95 % confidence interval [CI], 1.223-1.519; p = 2.140E-08) and LD (OR = 1.403; 95 % CI, 1.151-1.711; p = 8.226E-04). However, the analysis also revealed that there was no causal relationship between VaD (OR = 1.044; 95 % CI = 1.136-1.027; p = 0.316) and the risk of delirium. Additionally, our study does not provide evidence to support a causal correlation between delirium and the risk of developing any form of dementia. CONCLUSION The results of the MR analysis suggest a potential causal link between dementia and an increased risk of delirium. Nevertheless, it should be emphasized that the existing evidence does not provide support for a causal connection in the reverse direction, implying that delirium may not play a causative role in the onset of dementia.
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Affiliation(s)
- Zhongyuan Lu
- Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan Province 450000, China; Laboratory Animal Center, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450000, China
| | - Xiaoling Wang
- Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan Province 450000, China; Laboratory Animal Center, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450000, China
| | - Tian Mao
- Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan Province 450000, China; Laboratory Animal Center, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450000, China
| | - Lu Liu
- Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan Province 450000, China; Laboratory Animal Center, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450000, China
| | - Jiaqiang Zhang
- Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan Province 450000, China; Laboratory Animal Center, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450000, China.
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Golubovic J, Neerland BE, Simpson MR, Johansson K, Baker FA. A randomized pilot and feasibility trial of live and recorded music interventions for management of delirium symptoms in acute geriatric patients. BMC Geriatr 2025; 25:306. [PMID: 40316916 PMCID: PMC12048927 DOI: 10.1186/s12877-025-05954-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 04/17/2025] [Indexed: 05/04/2025] Open
Abstract
BACKGROUND Delirium is an acute shift in attention and arousal, usually triggered by acute illness or surgery in older dementia patients. Prognosis is poor, and pharmacological options are limited; non-pharmacological interventions and music show promise. METHODS This randomised pilot and feasibility trial tested feasibility, acceptability, fidelity, and safety of music interventions (MIs) for delirium patients and assessed preliminary effectiveness and suitability of the selected effect outcomes. Participants from an acute geriatric ward were randomised to Preferred Recorded Music (PRM) and Preferred Live Music (PLM), delivered for 30 min over three consecutive days. Feasibility outcomes included recruitment rate, retention, adherence, deviations, and treatment fidelity. Clinical outcomes were trajectory of delirium symptoms (arousal, attention, cognition), delirium duration, hospital stay length, and medication intake. Post-intervention and between groups changes in delirium symptoms were compared using mixed linear regression models for the repeated measurements. Mann-Whitney test and Fishers exact test were used for length of stay and medication use, respectively. RESULTS 26 participants (PLM = 14; PRM = 12), median age 87, most with hypoactive delirium were recruited at a rate of three participants per month. Retention rates for PLM and PRM were 64% and 33% respectively and adherence to PLM and PRM intervention protocols were 83% and 58%, respectively. Total adherence to the assessment protocols was 44%. PLM was delivered as intended, (treatment fidelity 93%), and PRM did not satisfy treatment fidelity (83%). All delirium symptoms except arousal improved on day 3 compared to baseline, with statistically significant improvement in attention. No conclusive pre-post or between-group differences were detected for any outcomes; confidence intervals were wide. CONCLUSIONS Feasibility of recruitment, interventions and assessments was indicated, and greater acceptability, safety and fidelity of the PLM intervention compared with the PRM. Adoption of external assessors is warranted in future trials, to mitigate slow recruitment and low adherence. Wide confidence intervals for most measures and comparisons indicate that the possible effect of the MIs on delirium cannot be excluded. The trial was registered at Clinical Trials, ID: NCT05398211, on 31/05/2022.
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Affiliation(s)
- Jelena Golubovic
- Centre for Research in Music and Health (CREMAH), Norwegian Academy of Music, Oslo, Norway.
- Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
- Faculty of Fine Arts and Music, The University of Melbourne, Melbourne, Australia.
| | - Bjørn Erik Neerland
- Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
| | - Melanie R Simpson
- Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
| | - Kjersti Johansson
- Centre for Research in Music and Health (CREMAH), Norwegian Academy of Music, Oslo, Norway
| | - Felicity A Baker
- Centre for Research in Music and Health (CREMAH), Norwegian Academy of Music, Oslo, Norway
- Faculty of Fine Arts and Music, The University of Melbourne, Melbourne, Australia
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Wang Q, Luan J, Yu W. Effects of sevoflurane and propofol for elderly patients: A systematic review and meta-analysis. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2025; 30:22. [PMID: 40391341 PMCID: PMC12087908 DOI: 10.4103/jrms.jrms_154_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 01/25/2025] [Accepted: 03/17/2025] [Indexed: 05/21/2025]
Abstract
Background To evaluate the safety of propofol and sevoflurane for general anesthesia in elderly. Materials and Methods All studies on sevoflurane, propofol, and hyperamylasemia from the establishment of Embase, Ovid, Cochrane Library, and Google Scholar from database establishment to December 2024 were searched. Literatures were screened, and data were extracted on the grounds of inclusion and exclusion criteria. Review Manager (RevMan) (Version 5.4. The Cochrane Collaboration.) was used for statistical analysis. Outcomes assessed included time to spontaneous eye opening, extubation time, incidence rate of postoperative cognitive dysfunction (POCD), postoperative delirium, agitation, nausea and vomiting. Results Fourteen trials were identified and included in this meta-analysis. The results showed no significant difference in time to spontaneous eye opening (P = 0.54), the incidence of POCD (P = 0.07), postoperative delirium (P = 0.37), and postoperative nausea and vomiting (P = 0.8) between the sevoflurane and propofol groups. Compared with propofol groups, extubation time (P < 0.0001) was significantly shortened by sevoflurane groups. Conversely, compared with sevoflurane, the incidence of postoperative agitation in the propofol group was significantly reduced (P = 0.04). Conclusion There was no difference in time to spontaneous eye-opening, the incidence of POCD, postoperative delirium, postoperative nausea, and vomiting between the sevoflurane and propofol groups. However, compared with propofol, sevoflurane can significantly shorten intubation time. The incidence of postoperative agitation (P = 0.04) was significantly lower in the propofol group compared with sevoflurane.
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Affiliation(s)
- Qi Wang
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, China
| | - Jing Luan
- Department of Pain, Tianjin First Central Hospital, Tianjin, China
| | - Wenli Yu
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, China
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11
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Tang C, Zhong J, Wang X, Zhu F, Wang B, Zhang Y, Hu D. Evaluating the Chinese versions of delirium assessment scales: a diagnostic systematic review. BMC Psychiatry 2025; 25:431. [PMID: 40296051 PMCID: PMC12039140 DOI: 10.1186/s12888-025-06745-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 03/19/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND The purpose of this study is to examine the validity, reliability and methodological quality of delirium scales that have been translated and adapted in China using quality assessment tools. METHODS A comprehensive search was conducted in PubMed, Embase, Web of Science, China Knowledge Network (CNKI), VIP database, Wanfang database, and China Biomedical Literature Database. The search covered the period from the establishment of the database until September 1, 2023. Two researchers independently screened the literature and extracted data. Studies were included if they focused on the translation of a delirium scale from English into simplified or traditional Chinese, with a study population aged ≥ 18 years and full text available. The risk of bias was assessed through the QUADAS-2 instrument. Level of evidence recommendation is completed with the GRADE and performed with GRADE GPT. Due to high heterogeneity across studies, a random-effects model was applied to calculate diagnostic accuracy indicators (sensitivity, specificity, and area under the curve index). This study has registered in the prospero. RESULTS Thirteen studies were included, of which 2 were case-control studies and 11 were cross-sectional studies. These studies involved 13 adult delirium assessment tools, and were all translated following the Brislin or ISPOR principle. The results of the methodological quality assessment showed that 3D-CAM, 4AT, CAM-ICU, CAM-ICU-7, and S-PTD had higher quality ratings, with 4AT being the highest quality. 4AT, CAM, 3D-CAM, CAM-CR, CAM-ICU, CAM-ICU-7, and Nu-DESC were recommended at a level B. The Cronbach's coefficient of most studies is over 0.8, and the inter-rater reliability of most studies is near or over 0.9, indicating good internal consistency and stability. Besides, a significant inverse correlation was found between these 13 Chinese-adapted delirium scales and their reference tests, with most studies were over 0.7, and especially 3 studies offered S-CVI and I-CVI value that were all larger than 0.9, indicating a good discriminate validity and content validity, though different cut-off points were recommended by different scales. Moreover, the sensitivity and specificity of these studies were mainly larger than 0.9, which proved the good diagnostic accuracy of these included scales. The pooled sensitivity of 7 Chinese delirium adaption scales that provided statistical data is 0.93 (95% CI: 0.89-0.96), and the pooled specificity is 0.94 (95% CI: 0.94-0.96), and the AUC is 0.98 (95% CI: 0.96-0.99). CONCLUSIONS The research on the Chinese adaptation of the delirium scale in China is relatively abundant and of acceptable quality. Taking into account factors of methodological quality and diagnostic accuracy, Chinese-adapted delirium assessment scales such as 3D-CAM, 4AT, CAM, CAM-ICU, CAM-ICU-7, and NuDESC appear to be suitable alternatives to the original English delirium scales and are recommended for use in primary care settings in China. Future research and continuous optimization are needed to improve the scientific rigor and accuracy of these tools, which will help advance the field. No Patient or Public Contribution is considered.
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Affiliation(s)
- Chen Tang
- Department of Nursing, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jun Zhong
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xiaojiao Wang
- Department of Nursing, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Fangfang Zhu
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Bei Wang
- Department of Nursing, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yanting Zhang
- Department of Intensive Care Unit, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Deying Hu
- Department of Nursing, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Lafuente-Lafuente C, Candia EH, Pautas E, Freund Y, Oquendo B, Belmin J. Development of a checklist for systematic screening of precipitating factors in older patients admitted to hospital with delirium. Eur Geriatr Med 2025:10.1007/s41999-025-01191-2. [PMID: 40253658 DOI: 10.1007/s41999-025-01191-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 03/11/2025] [Indexed: 04/22/2025]
Abstract
OBJECTIVES Causes of delirium are often multiple in older people and a significant number of them are missed at the initial assessment. We wanted to develop a checklist to help clinicians to systematically screen for the most frequent and important causes of delirium in this population. METHODS Three investigators, based on previous studies, drafted three possible checklist base models, comprising 18-29 items. A panel of 12 experts voted to choose one of the models, and then followed a modified Delphi consensus method to review each item and further develop the checklist. The consensus checklist was then tested in a small group of patients. The target population was older patients with delirium arriving to the emergency department or to a medical hospital ward. RESULTS The longest of the three drafts was unanimously chosen by the panel. After three rounds, a consensus was reached and a final checklist agreed. It is composed by 27 items organized in five groups of causes: infections, hydro-electrolytic disturbances, drugs, acute neurological conditions, and other acute diseases. A pilot study conducted by 15 physicians in 21 consecutive patients showed that the checklist was easy to complete, quick (mean 4 min) and most clinicians, though it helped them through the initial diagnostic work. CONCLUSIONS We have developed and pilot tested a checklist for screening for acute precipitants of delirium in older patients, aimed to facilitate early recognition and treatment of the multiple causes that often coexists in this population.
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Affiliation(s)
- Carmelo Lafuente-Lafuente
- Hôpital Charles Foix, Service de Gériatrie à orientation Cardiologique et Neurologique, Sorbonne Université, APHP, 7 avenue de la République, 94205, Ivry-sur-Seine, France.
- Clinical Epidemiology and Ageing (CEpiA) Team, Université Paris Est Créteil, INSERM, IRMB, 94000, Créteil, France.
| | | | - Eric Pautas
- Hôpital Charles Foix, Service de Gériatrie Aigue Polyvalente, Sorbonne Université, APHP, 94200, Ivry-sur-Seine, France
| | - Yonathan Freund
- Hôpitaux Universitaires Pitié-Salpêtrière, Service d'Accueil des Urgences, Sorbonne Université, APHP, 75013, Paris, France
| | - Bruno Oquendo
- Hôpital Charles Foix, Service de Gériatrie à orientation Cardiologique et Neurologique, Sorbonne Université, APHP, 7 avenue de la République, 94205, Ivry-sur-Seine, France
| | - Joël Belmin
- Hôpital Charles Foix, Service de Gériatrie à orientation Cardiologique et Neurologique, Sorbonne Université, APHP, 7 avenue de la République, 94205, Ivry-sur-Seine, France
- Laboratoire LIMICS, Sorbonne Université, Paris, France
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13
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Zhou X, Yin C. Comparison of the efficacy of pharmacological interventions for the prevention of delirium: A systematic review and network meta-analysis. Med Clin (Barc) 2025; 164:106918. [PMID: 40233662 DOI: 10.1016/j.medcli.2025.106918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 12/18/2024] [Accepted: 12/19/2024] [Indexed: 04/17/2025]
Abstract
BACKGROUND In recent years, many pharmacological agents for the prevention of delirium have emerged; however, the efficacy of these agents in preventing delirium remains unclear. OBJECTIVE To compare and rank the efficacy of different pharmacological interventions for the prevention of delirium. DESIGN A systematic review and network meta-analysis. METHODS Relevant randomized controlled trials on drug prevention of delirium were extracted from three electronic databases. A network meta-analysis was then conducted to assess the relative efficacy of drug interventions in preventing delirium. The quality of the data was evaluated using the Cochrane Risk of Bias tool. RESULTS A total of 80 randomized controlled trials on drug interventions were included in the final analysis. Treatment with dexmedetomidine can prevent delirium. CONCLUSION Dexmedetomidine treatment can prevent delirium and reduce patient suffering. Healthcare professionals should be encouraged to use dexmedetomidine for delirium prevention.
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Affiliation(s)
- Xiangwu Zhou
- Department of Cardiac Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Chengguo Yin
- Department of Cardiac Surgery, Wuhan Asian General Hospital, Wuhan, China.
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14
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Zhang W, Jin T, Hu X. Associations between triglyceride-glucose indices and delirium risk in critically ill patients with acute kidney injury: a retrospective study. Front Endocrinol (Lausanne) 2025; 16:1521850. [PMID: 40276552 PMCID: PMC12018253 DOI: 10.3389/fendo.2025.1521850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Accepted: 03/24/2025] [Indexed: 04/26/2025] Open
Abstract
Background Delirium frequently occurs in individuals with acute kidney injury (AKI), leading to serious adverse outcomes. However, there are currently no predictors of early intervention for delirium in clinical practice. This study aims to investigate whether a correlation exists between TyG indices and the clinical symptoms of delirium in patients with AKI. Methods Eligible participants diagnosed with AKI from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database were categorised based on their TyG index. The primary outcome of this study was the incidence of delirium. The TyG indices were quartile and Kaplan-Meier (K-M) cumulative curve was conducted to compare the consequence of each group. Cox proportional hazards and restricted cubic spline (RCS) analyses were employed to explore the associations between TyG indices and outcomes. To mitigate potential biases, a no-replacement propensity score matching (PSM) approach was employed. Subgroup analyses were conducted to explore differences across various demographic and clinical categories. Results A positive correlation between the quartile groupings of TyG-AVG and an increased cumulative incidence of delirium in individuals with severe AKI, as demonstrated through K-M cumulative curves and Cox regression analysis. Regarding the TyG index, patients in the 4th group displayed the highest hazard of delirium in both of the methods mentioned above. Furthermore, RCS analysis indicated that the interaction between the two variables is approximately linear. Subgroup analyses revealed that the effects of both metrics remained consistent across most examined subgroups. Conclusion Higher TyG indices were clearly associated with the incidence of delirium in patients with severe AKI. These indices could serve as valuable tools for identifying delirium-prone individuals with AKI.
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Affiliation(s)
- Wenhui Zhang
- School of Medicine, Anhui University of Science & Technology, Huainan, Anhui, China
- Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Huainan, Anhui, China
- Joint Research Center for Occupational Medicine and Health of Institute of Health and Medicine, Anhui University of Science and Technology, Huainan, Anhui, China
| | - Tao Jin
- School of Medicine, Anhui University of Science & Technology, Huainan, Anhui, China
- Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Huainan, Anhui, China
- Joint Research Center for Occupational Medicine and Health of Institute of Health and Medicine, Anhui University of Science and Technology, Huainan, Anhui, China
| | - Xinyue Hu
- School of Medicine, Anhui University of Science & Technology, Huainan, Anhui, China
- Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Huainan, Anhui, China
- Joint Research Center for Occupational Medicine and Health of Institute of Health and Medicine, Anhui University of Science and Technology, Huainan, Anhui, China
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15
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Molitor V, Seiters JC, Vollmar HC, Palm R. Development of a curriculum for interdisciplinary e-learning on delirium in nursing homes-a modified Delphi study. BMC MEDICAL EDUCATION 2025; 25:493. [PMID: 40197253 PMCID: PMC11977890 DOI: 10.1186/s12909-025-07078-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 03/28/2025] [Indexed: 04/10/2025]
Abstract
BACKGROUND Health care professionals (HCPs) in nursing homes, such as nurses and general practitioners (GPs), indicate a need for delirium-specific education. However, establishing educational interventions in the nursing home setting is challenging. e-learning is one method of compensating for these difficulties. Therefore, this study aims to develop a curriculum for interdisciplinary e-learning to improve delirium-specific knowledge in HCPs in nursing homes. METHODS Delirium-specific competencies were formulated on the basis of exploratory setting-independent literature. The competencies were assessed for relevance (very relevant, relevant, less relevant and not relevant) by an expert panel through a two-stage Delphi study that included an integrated workshop. A consensus was assumed if 80% of the experts rated a competence as very relevant or relevant in the first round. Competencies with approval ratings between 75% and 80% after the first round and/or that were critically commented upon were discussed in the subsequent workshop and assessed again in the second round. The competencies that received approval ratings below 75% in the first Delphi round were removed. In the second Delphi round, competencies that did not achieve at least 80% approval were ultimately excluded. RESULTS A total of 120 competencies were formulated, including 108 that addressed both disciplines, 4 addressed nurses, and 8 addressed GPs. Nineteen experts participated in the first Delphi round, after which n=92 (76.7%) of the competences were approved and n=18 (15%) were deleted. A total of 10 (8.3%) of the competencies were critically discussed by 10 experts in the subsequent workshop, of which 6 were deleted. Four competencies (3 addressed nurses and 1 GP) were evaluated by 11 experts in the second Delphi, 3 of which were confirmed (the competence addressing GPs was deleted). Overall, n=97 (81.2%) competencies were included in the final curriculum. Of these, n=64 (66%) addressed both disciplines, n=16 (16.5%) addressed nurses, and n=17 (17.5%) addressed GPs. CONCLUSIONS Delirium is an interdisciplinary challenge. Hence, the majority of our newly developed competencies address both disciplines. However, discipline-specific competencies must be addressed in the development of e-learning. A competence-based curriculum is a necessary basis for providing interdisciplinary e-learning for HCPs in nursing homes.
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Affiliation(s)
- Vincent Molitor
- School VI - School of Medicine and Health Sciences, Carl Von Ossietzky University, Oldenburg, Germany.
| | - Johanna Christina Seiters
- School VI - School of Medicine and Health Sciences, Carl Von Ossietzky University, Oldenburg, Germany
| | - Horst Christian Vollmar
- Institute of General Practice and Family Medicine (AM RUB), Medical Faculty, Ruhr University Bochum, Bochum, Germany
| | - Rebecca Palm
- School VI - School of Medicine and Health Sciences, Carl Von Ossietzky University, Oldenburg, Germany
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Park C, Han C, Jang SK, Kim H, Kim S, Kang BH, Jung K, Yoon D. Development and Validation of a Machine Learning Model for Early Prediction of Delirium in Intensive Care Units Using Continuous Physiological Data: Retrospective Study. J Med Internet Res 2025; 27:e59520. [PMID: 40173433 PMCID: PMC12004028 DOI: 10.2196/59520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 08/08/2024] [Accepted: 02/17/2025] [Indexed: 04/04/2025] Open
Abstract
BACKGROUND Delirium in intensive care unit (ICU) patients poses a significant challenge, affecting patient outcomes and health care efficiency. Developing an accurate, real-time prediction model for delirium represents an advancement in critical care, addressing needs for timely intervention and resource optimization in ICUs. OBJECTIVE We aimed to create a novel machine learning model for delirium prediction in ICU patients using only continuous physiological data. METHODS We developed models integrating routinely available clinical data, such as age, sex, and patient monitoring device outputs, to ensure practicality and adaptability in diverse clinical settings. To confirm the reliability of delirium determination records, we prospectively collected results of Confusion Assessment Method for the ICU (CAM-ICU) evaluations performed by qualified investigators from May 17, 2021, to December 23, 2022, determining Cohen κ coefficients. Participants were included in the study if they were aged ≥18 years at ICU admission, had delirium evaluations using the CAM-ICU, and had data collected for at least 4 hours before delirium diagnosis or nondiagnosis. The development cohort from Yongin Severance Hospital (March 1, 2020, to January 12, 2022) comprised 5478 records: 5129 (93.62%) records from 651 patients for training and 349 (6.37%) records from 163 patients for internal validation. For temporal validation, we used 4438 records from the same hospital (January 28, 2022, to December 31, 2022) to reflect potential seasonal variations. External validation was performed using data from 670 patients at Ajou University Hospital (March 2022 to September 2022). We evaluated machine learning algorithms (random forest [RF], extra-trees classifier, and light gradient boosting machine) and selected the RF model as the final model based on its performance. To confirm clinical utility, a decision curve analysis and temporal pattern for model prediction during the ICU stay were performed. RESULTS The κ coefficient between labels generated by ICU nurses and prospectively verified by qualified researchers was 0.81, indicating reliable CAM-ICU results. Our final model showed robust performance in internal validation (area under the receiver operating characteristic curve [AUROC]: 0.82; area under the precision-recall curve [AUPRC]: 0.62) and maintained its accuracy in temporal validation (AUROC: 0.73; AUPRC: 0.85). External validation supported its effectiveness (AUROC: 0.84; AUPRC: 0.77). Decision curve analysis showed a positive net benefit at all thresholds, and the temporal pattern analysis showed a gradual increase in the model scores as the actual delirium diagnosis time approached. CONCLUSIONS We developed a machine learning model for delirium prediction in ICU patients using routinely measured variables, including physiological waveforms. Our study demonstrates the potential of the RF model in predicting delirium, with consistent performance across various validation scenarios. The model uses noninvasive variables, making it applicable to a wide range of ICU patients, with minimal additional risk.
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Affiliation(s)
- Chanmin Park
- Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Changho Han
- Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Sora Kim
- Ajou University Hospital Gyeonggi South Regional Trauma Center, Suwon, Republic of Korea
| | - Byung Hee Kang
- Department of Surgery, Division of Trauma Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Kyoungwon Jung
- Department of Surgery, Division of Trauma Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Dukyong Yoon
- Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
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Itting PT, Sadlonova M, Santander MJ, Knierim M, Derad C, Asendorf T, Celano CM, Hansen N, Esselmann H, Heinemann S, Eberhard C, Hoteit M, Schröder MF, Kutschka I, Wiltfang J, von Arnim CAF, Baraki H. Intra- and early postoperative predictors of delirium risk in cardiac surgery: results from the prospective observational FINDERI study. Int J Surg 2025; 111:2872-2885. [PMID: 39903520 DOI: 10.1097/js9.0000000000002265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 01/09/2025] [Indexed: 02/06/2025]
Abstract
BACKGROUND Postoperative delirium (POD) is a severe complication following cardiac surgery and is associated with increased morbidity and mortality. The impact of intra- and early postoperative factors on the occurrence of POD following cardiac surgery remains controversial. To close this gap, we investigated intra- and early postoperative factors and their predictive values for POD. METHODS We performed a prospective observational study that aimed to FIND DElirium RIsk factors (FINDERI) for patients undergoing elective cardiac surgery. POD was assessed using the Confusion Assessment Method algorithm. Intra- and early postoperative factors were extracted from electronic medical records and reviewed by cardiac surgeons. To identify potential predictors of POD, we used univariate and multivariate logistic regression along with machine learning (ML) with ten-fold cross-validation. RESULTS In our study cohort of 490 patients, 106 screened positive for POD (21.6%). In the multivariate analysis, we found a positive association between POD occurrence and age ( P < 0.001), duration of surgery ( P = 0.027), combined (versus isolated) surgical procedures ( P = 0.024), opening of the cardiac chambers ( P = 0.046), and ventilation time ( P < 0.001). The ML-based decision tree identified a two level-algorithm including ventilation time and aortic cross-clamping time, with an AUC of 0.7116 ( P = 0.0002) in the validation set. In the ML-based LASSO regression analysis, we identified ventilation time, administration of erythrocyte concentrates (EC), and usage of cardiopulmonary bypass (CPB) as predictors of POD, with an AUC of 0.7407 ( P < 0.0001) in the validation set. CONCLUSION The results of this analysis highlight the associations between ventilation time, aortic cross-clamping time, administration of EC, and usage of CPB and POD. Additionally, they suggest that the optimization of surgical protocols has the potential to reduce POD risk in individuals undergoing cardiac surgery.
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Affiliation(s)
- Paul T Itting
- Department of Cardiovascular and Thoracic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
| | - Monika Sadlonova
- Department of Cardiovascular and Thoracic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
- Department of Geriatrics, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
- DZHK (German Center for Cardiovascular Research), partner site Lower Saxony, Germany
- Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Manuel J Santander
- Department of Cardiovascular and Thoracic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
- DZHK (German Center for Cardiovascular Research), partner site Lower Saxony, Germany
| | - Maria Knierim
- Department of Cardiovascular and Thoracic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
| | - Carlotta Derad
- Department of Medical Statistics, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
| | - Thomas Asendorf
- Department of Medical Statistics, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
| | - Christopher M Celano
- Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA
| | - Niels Hansen
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
| | - Hermann Esselmann
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
| | - Stephanie Heinemann
- Department of Geriatrics, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
| | - Charlotte Eberhard
- Department of Cardiovascular and Thoracic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
| | - Melanie Hoteit
- Department of Cardiovascular and Thoracic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
| | - Mirjam F Schröder
- Department of Cardiovascular and Thoracic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
| | - Ingo Kutschka
- Department of Cardiovascular and Thoracic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
- DZHK (German Center for Cardiovascular Research), partner site Lower Saxony, Germany
| | - Jens Wiltfang
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
- German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany
- Department of Medical Sciences, Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal
| | - Christine A F von Arnim
- Department of Geriatrics, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
- DZHK (German Center for Cardiovascular Research), partner site Lower Saxony, Germany
| | - Hassina Baraki
- Department of Cardiovascular and Thoracic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany
- DZHK (German Center for Cardiovascular Research), partner site Lower Saxony, Germany
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18
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Deng C, Jowsey T, Becker I, Campbell D, Hill J, Bhagvandas J, Fuchs R, Lightfoot NJ, Djamali K, Weller J. Patients' perceptions of brain health after surgery: a mixed-methods study of perioperative risk communication in older surgical patients in New Zealand. Br J Anaesth 2025; 134:1068-1076. [PMID: 39894749 PMCID: PMC11947577 DOI: 10.1016/j.bja.2024.12.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 12/26/2024] [Accepted: 12/27/2024] [Indexed: 02/04/2025] Open
Abstract
BACKGROUND We explored how adult surgical patients perceived their risk of major postoperative complications, including neurological complications, and how much information they wanted to receive about such risks. METHODS We undertook a mixed-methods study including a 13-item survey and thematic analysis of semi-structured interviews with patients undergoing noncardiac, non-neurologic surgery. RESULTS Of 557 distributed surveys, 547 were returned completed. Of these, 88% of respondents had previously undergone surgery. Respondents were most likely to indicate an extreme level of concern for major stroke (64%), followed by heart attack (56%), minor stroke (46%), and cognitive decline (43%). Women were more likely to indicate a higher level of concern for cognitive decline than men (odds ratio 1.6, 95% confidence interval 1.1-2.4, P=0.015). Seventeen people participated in interviews. Six themes were identified: (1) trust in healthcare professionals; (2) surgery to achieve hopes and ambitions; (3) previous experiences govern expectations and perception of risk; (4) positive outlook and spirituality as protective factors; (5) support matters; and (6) a personalised approach to risk discussion. CONCLUSIONS Many participants did not know the risks of major perioperative complications but based their risk perception on previous experiences and trust in health professionals. Participants focused on hope more than their concerns. Information provision should be personalised as patients expressed differences in the desired amount of information on risks.
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Affiliation(s)
- Carolyn Deng
- Department of Anaesthesia and Perioperative Medicine, Te Toka Tumai Auckland, Auckland, New Zealand; Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
| | - Tanisha Jowsey
- Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia
| | - Ines Becker
- Department of Anaesthesia and Perioperative Medicine, Te Toka Tumai Auckland, Auckland, New Zealand
| | - Doug Campbell
- Department of Anaesthesia and Perioperative Medicine, Te Toka Tumai Auckland, Auckland, New Zealand; Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Jack Hill
- Department of Anaesthesia and Perioperative Medicine, Te Toka Tumai Auckland, Auckland, New Zealand
| | - Jignal Bhagvandas
- Department of Anaesthesia, Whangārei Hospital, Whangārei, New Zealand
| | - Ralph Fuchs
- Department of Anaesthesia, Whangārei Hospital, Whangārei, New Zealand
| | - Nicholas J Lightfoot
- Department of Anaethesia and Pain Medicine, Middlemore Hospital, Auckland, New Zealand
| | - Kaveh Djamali
- Department of Anaethesia and Pain Medicine, Middlemore Hospital, Auckland, New Zealand
| | - Jennifer Weller
- Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
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Arai N, Sugiura Y, Nakajima S, Wada M, Moriyama S, Mimura Y, Niinomi K, Takayama K, Maeda R, Kitada S, Fagarasan S, Tajima M, Boku S, Takebayashi M, Kato J, Kitago M, Kitagawa Y, Takahashi T, Shimizu H, Uchida H, Suematsu M, Mimura M, Noda Y. Prediction of postoperative delirium by blood metabolome analysis. J Psychiatr Res 2025; 184:500-514. [PMID: 40153971 DOI: 10.1016/j.jpsychires.2025.03.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 02/27/2025] [Accepted: 03/20/2025] [Indexed: 04/01/2025]
Abstract
No established blood markers can preoperatively predict postoperative delirium. Blood concentrations of amino acid catabolites and dipeptides, including those secreted extracellularly during T-lymphocyte activation, were investigated as predictors of postoperative delirium using metabolomic analyses to ascertain whether preoperative blood metabolites could predict postoperative delirium. Eighteen and 24 participants were included in the delirium and non-delirium groups, respectively. Higher preoperative levels of amino acid (tryptophan) catabolites, via the indoleamine 2,3-dioxygenase pathway, were observed in the delirium group and identified as potential predictors of postoperative delirium in this study. The delirium group had preoperatively elevated levels of tryptophan catabolites and only a limited increase postoperatively, suggesting that the tryptophan catabolic pathway may be activated preoperatively in patients at high risk of delirium. Non-targeted metabolomic analysis found a set of preoperatively elevated γ-glutamyl dipeptides as potential predictors of postoperative delirium. In vitro experiments showed that T-cell-receptor stimulation increases tryptophan metabolism and specific γ-glutamyl dipeptide secretion, offering a possible explanation for the increased levels of metabolites in postoperative delirium. This study showed that levels of amino acid metabolites associated with blood immune activity may have the potential to predict postoperative delirium.
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Affiliation(s)
- Naohiro Arai
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yuki Sugiura
- Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shinichiro Nakajima
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
| | - Masataka Wada
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
| | - Sotaro Moriyama
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Yu Mimura
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Kanta Niinomi
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Kousuke Takayama
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Rae Maeda
- Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Seri Kitada
- Faculty of Medicine, Kyoto University, Kyoto, Japan
| | - Sidonia Fagarasan
- Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Masaki Tajima
- Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shuken Boku
- Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Minoru Takebayashi
- Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Jungo Kato
- Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Tatsuo Takahashi
- Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Hideyuki Shimizu
- Department of Cardiovascular Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Hiroyuki Uchida
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Makoto Suematsu
- Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan; Central Institute for Experimental Animals, Kawasaki, Japan
| | - Masaru Mimura
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Yoshihiro Noda
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
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Cong P, Huang X, Zhang Q, He M, Wan H, Wu Q, Wu H, Zhang Y, Cheng C, Tian L, Xiong L. DNMT3a Deficiency Contributes to Anesthesia/Surgery-Induced Synaptic Dysfunction and Cognitive Impairment in Aged Mice. Aging Cell 2025; 24:e14458. [PMID: 39722450 PMCID: PMC11984699 DOI: 10.1111/acel.14458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 11/26/2024] [Accepted: 12/05/2024] [Indexed: 12/28/2024] Open
Abstract
Perioperative neurocognitive disorder (PND) is a severe postoperative complication in older patients. Epigenetic changes are hallmarks of senescence and are closely associated with cognitive impairment. However, the effects of anesthesia and surgery on the aging brain's epigenetic regulatory mechanisms and its impact on cognitive impairment remain unclear. Using a laparotomy PND model, we report significant reduction in DNA methyltransferase 3a (DNMT3a) in hippocampal neurons of aged mice, which causes global DNA methylation decrease. Knockdown of DNMT3a leads to synaptic disorder and memory impairment in aged mice. Mechanistically, bisulfite sequencing revealed that DNMT3a deficiency reduces methylation in the LRG1 promoter region and promotes its transcription. We also show that activation of TGF-β signaling by the increase in LRG1 level, ultimately impacts the synaptic function. In contrast, both overexpressing DNMT3a or knockdown LRG1 in hippocampus can attenuate the synaptic disorders and rescue postoperative cognitive deficits in aged mice. Our results reveal that DNMT3a is a previously undefined mediator in the pathogenesis of PND, which couples epigenetic regulations with anesthesia/surgery-induced synaptic dysfunction and represents a therapeutic target to tackle PND.
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Affiliation(s)
- Peilin Cong
- Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain‐Like Intelligence, Shanghai Fourth People's Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Xinwei Huang
- Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain‐Like Intelligence, Shanghai Fourth People's Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Qian Zhang
- Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain‐Like Intelligence, Shanghai Fourth People's Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Mengfan He
- Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain‐Like Intelligence, Shanghai Fourth People's Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Hanxi Wan
- Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain‐Like Intelligence, Shanghai Fourth People's Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Qianqian Wu
- Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain‐Like Intelligence, Shanghai Fourth People's Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Huanghui Wu
- Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain‐Like Intelligence, Shanghai Fourth People's Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Yuxin Zhang
- Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain‐Like Intelligence, Shanghai Fourth People's Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Chun Cheng
- Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain‐Like Intelligence, Shanghai Fourth People's Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Li Tian
- Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain‐Like Intelligence, Shanghai Fourth People's Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Lize Xiong
- Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain‐Like Intelligence, Shanghai Fourth People's Hospital, School of MedicineTongji UniversityShanghaiChina
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21
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Mclean A, Ewens B, Towell-Barnard A. Delirium in the Acute Care Setting From the Families Perspective: A Scoping Review. J Adv Nurs 2025. [PMID: 40159700 DOI: 10.1111/jan.16891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 02/13/2025] [Accepted: 02/28/2025] [Indexed: 04/02/2025]
Abstract
AIM To explore the existing literature on delirium within the acute care setting from the family members' perspective and summarise key findings. DESIGN A scoping review guided by Arksey and O'Malley's methodological framework and refined by the Joanna Briggs Institute. REVIEW METHODS The Population, Concept, and Context framework recommended by the Joanna Briggs Institute's scoping review protocol identified the main concepts in the primary review question. The inclusion criteria focused on primary research studies from any chronological date that explored the family members' experience of delirium within the acute care setting. Following screening by two independent reviewers, data extraction was conducted and presented in tabular form, detailing the study aim, sample, setting, methods, key findings and recommendations for future research and clinical practice. DATA SOURCES A comprehensive search was conducted in January 2025 using CINAHL+, MEDLINE, JBI, Cochrane Library, Web of Science, Scopus and Google Scholar. Citation searching and reference lists supplemented this review to identify relevant studies. RESULTS Seventeen studies met the inclusion criteria. Families' experiences of delirium were categorised into (1) lack of awareness and understanding of delirium; (2) communication and informational needs of family members regarding delirium; (3) the emotional impact delirium has on family members, and (4) family desire to participate in their loved one's care. CONCLUSION This review highlighted a paucity of literature addressing the experiences of family members who witness delirium in the acute care setting. The existing research underscored the need for clear communication and information regarding delirium to mitigate the negative emotional impact that delirium places on families. IMPACT This scoping review provides insights into the challenges facing families witnessing delirium in the acute care setting. A better understanding of family members' experiences can guide the development of a supported family-centred approach to delirium care. PATIENT CONTRIBUTION No patient/public contribution.
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Affiliation(s)
- Amber Mclean
- Edith Cowan University, Perth, Western Australia, Australia
| | - Beverley Ewens
- School of Nursing and Midwifery, Edith Cowan University, Perth, Western Australia, Australia
| | - Amanda Towell-Barnard
- School of Nursing and Midwifery, Edith Cowan University, Perth, Western Australia, Australia
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22
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Fallon JM, Hashemaghaie M, Peterson CE, Tran D, Wu SR, Valdes JM, Pedicini NM, Adams ME, Soltis M, Mansour W, Wright MC, Raghunathan K, Treggiari MM, Sasannejad C, Devinney MJ. Protocol and design of the REPOSE study: a double-blinded, randomised, placebo-controlled trial to evaluate the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older patients undergoing non-cardiac surgery. BMJ Open 2025; 15:e091099. [PMID: 40081971 PMCID: PMC11907038 DOI: 10.1136/bmjopen-2024-091099] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 02/14/2025] [Indexed: 03/16/2025] Open
Abstract
INTRODUCTION Postoperative delirium occurs in up to 40% of older surgical patients and has been associated with prolonged hospital stays, long-term cognitive impairment and increased 1-year postoperative mortality. Postoperative sleep disturbances may increase the risk of delirium, but studies investigating pharmacotherapies to improve postoperative sleep to prevent delirium remain limited. Suvorexant is a selective antagonist of orexin 1 and 2 receptors and is approved for insomnia pharmacotherapy by the Food and Drug Administration. It has the potential to improve postoperative sleep and reduce postoperative delirium rates, but randomised controlled trials (RCTs) are needed to determine the efficacy of postoperative suvorexant administration. The REPOSE study (reducing delirium by enhancing postoperative sleep with suvorexant) is a single-centre, randomised, double-blinded RCT that aims to evaluate the efficacy of suvorexant in increasing total sleep time (TST) and decreasing delirium severity in older patients undergoing non-cardiac surgery. METHODS AND ANALYSIS REPOSE will enroll 130 patients (aged ≥65 years) undergoing non-cardiac surgery with a planned postoperative inpatient stay. Participants will be randomised to receive 20 mg oral suvorexant or placebo nightly on postoperative nights 0, 1 and 2. The primary endpoint is TST on the first postoperative night, as measured using an electroencephalography headband. The secondary endpoint is peak postoperative delirium severity as measured by the 3-minute diagnostic interview for the confusion assessment method severity scores. Primary endpoint data will be analysed with a two-sample t-test using an intent-to-treat approach to compare TST on the first night that a patient received a study drug dose. Secondary and exploratory endpoint data will be analysed using two-sample t-tests between groups. ETHICS AND DISSEMINATION Ethical approval was obtained from the Duke Institutional Review Board (protocol #00111869). Results of the REPOSE study will be published in a peer-reviewed journal and presented at academic conferences. Trial data will be deposited in ClinicalTrials.gov. TRIAL REGISTRATION NUMBER NCT05733286.
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Affiliation(s)
- John Michael Fallon
- Duke University, Trinity College of Arts and Sciences, Durham, North Carolina, USA
| | - Mona Hashemaghaie
- Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Christy E Peterson
- Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Dieplinh Tran
- Louisiana State University School of Medicine, New Orleans, Louisiana, USA
| | - Sophie R Wu
- Duke University Pratt School of Engineering, Durham, North Carolina, USA
| | - Jonathan M Valdes
- Duke University, Trinity College of Arts and Sciences, Durham, North Carolina, USA
| | - Nicole M Pedicini
- Duke University, Trinity College of Arts and Sciences, Durham, North Carolina, USA
| | - Melissa E Adams
- Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Marjorie Soltis
- Department of Neurology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Wissam Mansour
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Mary Cooter Wright
- Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Karthik Raghunathan
- Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Miriam M Treggiari
- Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Cina Sasannejad
- Department of Neurology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Michael J Devinney
- Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA
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23
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Suh JM, Raykageeraroj N, Waldman B, Kitisin N, Haywood C, Bellomo R, Koshy AN, Pilcher D, Lee DK, Weinberg L. Characteristics, outcomes, and complications among nonagenarian and centenarian patients admitted to the intensive care unit: a scoping review. Crit Care 2025; 29:112. [PMID: 40083001 PMCID: PMC11907827 DOI: 10.1186/s13054-025-05349-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 02/28/2025] [Indexed: 03/16/2025] Open
Abstract
INTRODUCTION Nonagenarians and centenarians are a growing and vulnerable groups of patients admitted to ICU. There is limited information on their characteristics, outcomes, and complications. METHODS We performed a scoping review of studies focused on nonagenarians and centenarians admitted to ICU. We assessed their characteristics, the presence of frailty, the presence of comorbidities, their complications, their ICU and hospital length of stay and mortality and their long-term outcomes. RESULTS We assessed 36 studies, mostly retrospective, with one classified as a National Quality Registry study and another as a prospective analysis of two large multinational cohorts. The studies involved 16,859 patients with a mean age of 92.4 years and a male prevalence of 39.3%. Multiple comorbidities were present in the majority of patients. Overall, 40.7% of patients received mechanical ventilation, with a median of 36% (range: 0%-100%; IQR: 23.8%-50%). Mean duration of mechanical ventilation was 90.4 h, with a median of 84 h (range: 10-221 h; IQR: 12.25-146.5 h). Cardiovascular and renal complications were common. Mean ICU stay across studies was 5.4 days, with a median of 5 days (range: 0.9-13 days; IQR: 2.55-7.03 days). The median length of hospital stay was 12.4 days (range: 5.7-31 days; IQR: 11-17.6 days). The median hospital mortality was 25.55% (range: 0%-62.5%; IQR: 15%-35.5%). The mean six-month and 1-year mortality rates were 38.6% and 45.6%, respectively. CONCLUSIONS Nonagenarians and centenarians admitted to ICU are a highly comorbid and vulnerable population who experience prolonged hospital stays and complications. However four out of five survive to hospital discharge and half are alive at one year after admission. Therefore, through judicious patient selection, ICU care can be both meaningful and beneficial. Our findings underscore the need for a standardized reporting structure for nonagenarians and centenarians admitted to the ICU to allow comparability across studies, enhanced data quality and reliability, greater research efficiency, and better identification of the unique health needs in this vulnerable patient cohort.
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Affiliation(s)
- Je Min Suh
- Department of Anaesthesia, Austin Health, 154 Studley Road, Heidelberg, VIC, 3084, Australia
| | - Nattaya Raykageeraroj
- Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Boris Waldman
- Department of Anaesthesia, Austin Health, 154 Studley Road, Heidelberg, VIC, 3084, Australia
| | - Nuanprae Kitisin
- Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Cilla Haywood
- Department of Geriatric Medicine, Austin Health, Heidelberg, Australia
- Department of Intensive Care, Austin Health, Heidelberg, Australia
| | - Rinaldo Bellomo
- Department of Intensive Care, Austin Health, Heidelberg, Australia
- Department of Critical Care, The University of Melbourne, Melbourne, VIC, Australia
| | - Anoop N Koshy
- Department of Cardiology, Austin Health, Heidelberg, Australia
| | - David Pilcher
- Department of Intensive Care, Alfred Health, Prahran, Australia
- Australian and New Zealand Intensive Care Research Centre, Monash University, Prahran, Australia
| | - Dong-Kyu Lee
- Department of Anaesthesiology and Pain Medicine, Dongguk University Ilsan Hospital, Goyang, Republic of Korea
| | - Laurence Weinberg
- Department of Anaesthesia, Austin Health, 154 Studley Road, Heidelberg, VIC, 3084, Australia.
- Department of Critical Care, The University of Melbourne, Melbourne, VIC, Australia.
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24
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Lia T, Yua C, Lv F, Feng Z, Hou Y, Ren L, Li P. The effect of perioperative cognitive training on postoperative delirium in older patients undergoing total hip and knee arthroplasty: a prospective randomised trial. Age Ageing 2025; 54:afaf020. [PMID: 40057984 DOI: 10.1093/ageing/afaf020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 02/26/2025] [Indexed: 03/29/2025] Open
Abstract
OBJECTIVE This study investigated whether cognitive training (CT) ameliorates postoperative delirium (POD) in older patients undergoing total hip and knee arthroplasty. METHODS This clinical trial was conducted from 18 February to 10 July 2023 and included individuals aged 60-79 who underwent elective total hip and knee arthroplasties with surgery durations ≤3 hours under general anaesthesia. Patients with preoperative cognitive dysfunction and dementia were excluded. The incidence of POD was compared between the CT and routine care (RC) groups as the primary outcome. Secondary outcomes included adverse events, postoperative pain within 48 hours, and POD characteristics. RESULTS In this study, 122 individuals were divided into two groups. The overall incidence of POD was 8.2% (10 out of 122), with no significant difference between the two groups (9.8% for CT group vs. 6.6% for RC group; P = .509). Secondary outcomes also showed no significant difference between the two groups. The training time was less, and the compliance rate was poor in the CT group (4.0%). Nonetheless, the results revealed a significant difference in POD rates among CT subgroups, and a robust correlation was identified between CT sessions lasting less than the median duration of 12 minutes and the incidence of POD (P = .043). CONCLUSION The incidence of POD in older patients undergoing total hip or knee arthroplasty may not be mitigated by CT. As POD was exclusively observed in patients with fewer CT sessions, it suggests that the compliance-recommended CT sessions may contribute to the POD.
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Affiliation(s)
- Ting Lia
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chang Yua
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Feng Lv
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhen Feng
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yan Hou
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Li Ren
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ping Li
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Zhang Q, Botta R, Xu Y, Wei JCC, Tung TH. Risk of new-onset dementia following COVID-19 infection: a systematic review and meta-analysis. Age Ageing 2025; 54:afaf046. [PMID: 40037563 DOI: 10.1093/ageing/afaf046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 02/11/2025] [Indexed: 03/06/2025] Open
Abstract
BACKGROUND Emerging evidence suggests coronavirus disease 2019 (COVID-19) infection may increase the risk of developing dementia, although studies have reported conflicting findings. This meta-analysis aimed to synthesise the literature on the association between COVID-19 and the risk of new-onset dementia. METHODS PubMed, Embase and Web of Science were searched for cohort studies or case-control studies that investigated new-onset dementia development among adult COVID-19 survivors compared to individuals without COVID-19 infection from inception to 9 November 2023. Studies that exclusively involved populations younger than 18 years, with known dementia or lacked adequate data about the risk of dementia were excluded. Two authors independently conducted the screening of eligible studies, data extraction and risk of bias assessment. The primary outcome was new-onset dementia following COVID-19 infection. Data were pooled using random-effects models, with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated. RESULTS A total of 15 retrospective cohort studies encompassing 26 408 378 participants were included. Pooled analysis indicated COVID-19 was associated with an increased risk of new-onset dementia (HR = 1.49, 95% CI: 1.33-1.68). This risk remained elevated when compared with non-COVID cohorts (HR = 1.65, 95% CI: 1.39-1.95), and respiratory tract infection cohorts (HR = 1.29, 95% CI: 1.12-1.49), but not influenza or sepsis cohorts. Increased dementia risk was observed in both males and females, as well as in individuals older than 65 years (HR = 1.68, 95% CI: 1.48-1.90), with the risk remaining elevated for up to 24 months. CONCLUSION This meta-analysis demonstrates a significant association between COVID-19 infection and increased risk of developing new-onset dementia, which underscores the need for cognitive monitoring and early intervention for COVID-19 survivors to address potential long-term neurological impacts.
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Affiliation(s)
- Qianru Zhang
- Department of Rheumatology and Immunology, Tsinghua University Affiliated Beijing Tsinghua Changgung Hospital, Beijing, China
- Harvard Medical School, Boston, MA 02115-6027, USA
| | | | - Ying Xu
- Tsinghua University, Beijing, China
- Evidence-based Medicine Center, Taizhou Hospital of Zhejiang Province, Linhai, Zhejiang, China
| | - James Cheng-Chung Wei
- Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
- Department of Nursing, Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- China Medical University Hospital - Graduate Institute of Integrated Medicine, Taichung, Taiwan
- Office of Research and Development, Asia University, Taichung, Taiwan
| | - Tao-Hsin Tung
- Evidence-based Medicine Center, Taizhou Hospital of Zhejiang Province, Linhai, Zhejiang, China
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Yamagata H, Kobayashi R, Hirose K, Seki T, Takihara T. Medical staff's knowledge of delirium by occupation and the effectiveness of an on-demand e-learning. PCN REPORTS : PSYCHIATRY AND CLINICAL NEUROSCIENCES 2025; 4:e70078. [PMID: 40094099 PMCID: PMC11910968 DOI: 10.1002/pcn5.70078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 02/06/2025] [Accepted: 02/23/2025] [Indexed: 03/19/2025]
Abstract
Aim We aimed to evaluate the understanding of delirium among multidisciplinary medical staff and assess whether a brief e-learning course improved their knowledge on the topic. Methods A total of 611 medical staff members participated in the study, including 32 physicians, 393 nurses, 33 nursing assistants, 21 pharmacists, and 132 other multidisciplinary staff, which included non-clinical personnel. A 20-question delirium knowledge test was administered both before and after a 40-min, on-demand e-learning course. Results At baseline, there was limited understanding that delirium involves a disturbance of consciousness, can be triggered by physical illness or medications, and that few medications are recommended for its treatment. Furthermore, visual hallucinations were not widely recognized as a common type of hallucination in delirium. However, care strategies and non-pharmacological interventions for delirium were well understood even before the course. After the brief e-learning course, knowledge scores significantly increased, demonstrating a large effect size of 0.53. Physicians and pharmacists achieved higher overall knowledge scores after the course compared to other occupational groups. Conclusion Education and targeted dissemination efforts regarding the causes, diagnosis, and pharmacological treatment of delirium are essential for enhancing delirium knowledge among multidisciplinary staff. The leadership role of a "liaison" psychiatrist is pivotal for ensuring effective delirium care and fostering a team-based approach in clinical practice.
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Affiliation(s)
- Hirotaka Yamagata
- Kokoro Hospital Machida Machida Japan
- Department of Psychiatry Ebina General Hospital Ebina Japan
- Department of Internal Medicine Hirose Hospital Sagamihara Japan
| | | | - Kenichi Hirose
- Department of Internal Medicine Hirose Hospital Sagamihara Japan
| | | | - Takahisa Takihara
- Department of Respiratory Medicine Ebina General Hospital Ebina Japan
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Ahmed MT, Troyas C, Daramola AM, Isik OG, Cassim TZ, Goldberg TE, Banerji A, Sleigh J, García PS. Characterization of Speech and Language Deficits in the Postanesthesia Care Unit: A Novel, Qualitative Cognitive Assessment. Anesth Analg 2025; 140:655-664. [PMID: 39976622 DOI: 10.1213/ane.0000000000006940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2025]
Abstract
BACKGROUND Assessing recovery after general anesthesia is complicated because patients must be sufficiently arousable to pay attention to the verbal instructions probing cognitive function. All delirium screens that have been used in the postanesthesia care unit (PACU) rely heavily on a patient's ability to process language information and respond appropriately. However, postanesthesia effects on speech-language functions have not been specifically evaluated. Here we present a novel, qualitative PACU evaluation for cognitive domains critical for speech-language functions, and we compare this assessment against a multidomain neurocognitive examination: Telephonic Montreal Cognitive Assessment (t-MoCA). This may be used to identify trajectories of neurocognitive recovery after surgery with general anesthesia and provide neuroanatomic correlates for specific deficits. METHODS We investigated 48 patients undergoing general anesthesia for noncardiac and nonneurologic elective surgeries. Preoperatively, participants were administered our PACU speech-language assessment (PACU-SLA) and t-MoCA. Both assessments were again administered postoperatively in the PACU. Different versions of PACU-SLA were administered pre- versus postoperatively. Twenty-three participants randomly received the same t-MoCA versions (group AA), and 25 participants received different versions (group AB), pre- versus postoperatively. Assessments were administered ≥30 minutes after PACU arrival, and before PACU discharge. Statistical analysis was performed using Wilcoxon-signed-rank tests for nonnormally distributed paired data, analysis of covariance for assessing the impact of group (AA versus AB) and preoperative scores on postoperative scores, and χ2 tests for unpaired categorical data (P < .05 indicating significance). RESULTS After adjusting for preoperative scores, the postoperative t-MoCA scores of group AB were significantly lower than group AA (F[1-46] = 21.7, P < .001). Similarly, the t-MoCA scores of episodic-memory (delayed-recall) decreased in group AB (F[1-46] = 48.6, P < .001). For PACU-SLA, there were no postoperative changes in auditory-comprehension and object-naming scores, but a decrease was observed in (1) scores of a 9-point narrative-production task of expressive-fluency (n = 48; median [25th-75th]; preoperative: 9[9-9], postoperative: 7[7-8], P < .001), and (2) total words generated in 2 30-second tasks of verbal-fluency (n = 48; median[25th-75th]: preoperative: 23[12.5-33.5], postoperative: 16.5[9.5-26.5], P < .001). Scores on a 4-point sentence-repetition task were also noted to decrease postoperatively (n = 48; median[25th-75th]; preoperative: 4[3-4], postoperative: 4[3-4], P = .04). When grouping participants by preoperative cognitive status (pMCI, n = 9; preoperative normal, n = 39), both groups showed postoperative changes in verbal-fluency (F[1-46] = 6.97, P = .01) and narrative-production scores (F[1-46] = 5.51, P = .02). CONCLUSIONS The PACU-SLA revealed lower fluency (hypophonia) with relatively intact comprehension, naming, and repetition, during recovery from general anesthesia. These deficits share features with transcortical motor aphasia.
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Affiliation(s)
- Meah T Ahmed
- From the Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York
| | - Carla Troyas
- From the Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York
| | - Alice M Daramola
- From the Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York
| | - Oliver G Isik
- From the Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York
| | - Tuan Z Cassim
- From the Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York
- Department of Psychology, College of Social and Behavioral Science, The University of Utah, Salt Lake City, Utah
| | - Terry E Goldberg
- From the Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York
| | - Antara Banerji
- Department of Anesthesia, Waikato Clinical Campus, University of Auckland, Auckland, New Zealand
| | - Jamie Sleigh
- Department of Psychology, College of Social and Behavioral Science, The University of Utah, Salt Lake City, Utah
| | - Paul S García
- From the Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York
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Khaled M, Chui J, Ewusie J, Agzarian J, Bogach J, Gomez M, Shayegan B, Shargall Y, Alkhamesi N, Paul J, Thabane L, Shanthanna H. Melatonin for preventing postoperative delirium in elderly patients: A multicenter randomized placebo-controlled pilot study. Medicine (Baltimore) 2025; 104:e41615. [PMID: 39998812 PMCID: PMC11856979 DOI: 10.1097/md.0000000000041615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/27/2025] [Accepted: 02/03/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Postoperative delirium (POD) in older adults is associated with high risk of morbidity and mortality. With limited treatment options, prevention is essential. Melatonin has been suggested to prevent delirium through regulating the sleep-wake cycle and serotonin metabolism, which has been shown to be disrupted in patients with POD. However, the evidence regarding the use of melatonin for POD prevention is limited and inconclusive. METHODS Our multicenter, 2-arm, parallel-group, feasibility randomized controlled trial evaluated the effect of melatonin on POD incidence after noncardiac surgery in patients >65 years (n = 120). Patients were randomized to 3 mg oral melatonin or placebo once preoperatively and for 7 days postoperatively. Patients were assessed twice daily for delirium and followed at 3 months postoperatively. Feasibility outcomes were recruitment rate, medication adherence, and proportion completing 3-month follow-up. Clinical outcomes were delirium incidence, sleep quality, institutional discharge, and cognitive status at 3 months. RESULTS Between September 2021 and June 2023, 85 patients were randomized (~1 patient/wk); of these, 92.9% adhered to study medications and 87.1% completed the 3-month follow-up. POD occurred in 9 patients with no statistical difference between the groups (melatonin group, n = 7; placebo group, n = 2; adjusted odds ratio: 1.12; 95% confidence interval: 0.006-150.1). There were no differences in any other clinical outcomes. Pandemic-related challenges, including interruption of surgeries and restrictions on research procedures impacted feasibility and the study was terminated early due to futility. CONCLUSIONS Based on our observations, a sample size of >1000 patients is required for a definitive trial to evaluate the role of melatonin in reducing the incidence of POD. Design changes need to be considered to address feasibility challenges and ongoing post-pandemic modifications to patient care.
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Affiliation(s)
- Maram Khaled
- Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
- Perioperative and Surgery Research Program, Population Health Research Institute, Hamilton, Ontario, Canada
| | - Jason Chui
- Department of Anesthesia and Perioperative Medicine, Western University, University Hospital, London, Ontario, Canada
| | - Joycelyne Ewusie
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - John Agzarian
- Department of Surgery, St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada
| | - Jessica Bogach
- Department of Surgery, McMaster University, Institute for Applied Health Sciences (4th Floor), Hamilton, Ontario, Canada
| | - Maria Gomez
- Department of Anesthesia and Perioperative Medicine, Western University, University Hospital, London, Ontario, Canada
| | - Bobby Shayegan
- Department of Surgery, McMaster University, Institute for Applied Health Sciences (4th Floor), Hamilton, Ontario, Canada
| | - Yaron Shargall
- Department of Surgery, McMaster University, Institute for Applied Health Sciences (4th Floor), Hamilton, Ontario, Canada
| | - Nawar Alkhamesi
- Department of Surgery, Western University, 268 Grosvenor Street, St. Joseph’s Hospital Rm. E3-118, London, Ontario, Canada
| | - James Paul
- Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Lehana Thabane
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Harsha Shanthanna
- Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
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Krewulak K, Strayer K, Jaworska N, Spence K, Foster N, Kupsch S, Sauro K, Fiest KM. Evaluation of the Quality of Delirium Website Content for Patient and Family Education: Cross-Sectional Study. J Med Internet Res 2025; 27:e53087. [PMID: 39977019 PMCID: PMC11888015 DOI: 10.2196/53087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 03/27/2024] [Accepted: 01/16/2025] [Indexed: 02/22/2025] Open
Abstract
BACKGROUND Patients and families who have experienced delirium may seek information about delirium online, but the quality and reliability of online delirium-related websites are unknown. OBJECTIVE This study aimed to identify and evaluate online delirium-related websites that could be used for patient and family education. METHODS We searched Microsoft Bing, Google, and Yahoo using the keywords "delirium" and the misspelled "delerium" to identify delirium-related websites created to inform patients, families, and members of the public about delirium. The quality of identified delirium-related website content was evaluated by 2 authors using the validated DISCERN tool and the JAMA (Journal of the American Medical Association) benchmark criteria. Readability was assessed with the Simple Measure of Gobbledygook, the Flesch Reading Ease score, and the Flesch Kincaid grade level. Each piece of website content was assessed for its delirium-related information using a checklist of items co-designed by a working group, which included patients, families, researchers, and clinicians. RESULTS We identified 106 websites targeted toward patients and families, with most hospital-affiliated (21/106, 20%) from commercial websites (20/106, 19%), government-affiliated organizations (19/106, 18%), or from a foundation or advocacy group (16/106, 15%). The median time since the last content update was 3 (IQR 2-5) years. Most websites' content (101/106, 95%) was written at a reading level higher than the recommended grade 6 level. The median DISCERN total score was 42 (IQR 33-50), with scores ranging from 20 (very poor quality) to 78 (excellent quality). The median delirium-related content score was 8 (IQR 6-9), with scores ranging from 1 to 12. Many websites lacked information on the short- and long-term outcomes of delirium as well as how common it is. The median JAMA benchmark score was 1 (IQR 1-3), indicating the quality of the websites' content had poor transparency. CONCLUSIONS We identified high-quality websites that could be used to educate patients, families, or the public about delirium. While most delirium-related website content generally meets quality standards based on DISCERN and JAMA benchmark criteria, high scores do not always ensure patient and family-friendliness. Many of the top-rated delirium content were text-heavy and complex in layout, which could be overwhelming for users seeking clear, concise information. Future efforts should prioritize the development of websites with patients and families, considering usability, accessibility, and cultural relevance to ensure they are truly effective for delirium education.
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Affiliation(s)
- Karla Krewulak
- Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada
| | - Kathryn Strayer
- Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada
| | - Natalia Jaworska
- Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada
| | - Krista Spence
- Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada
| | - Nadine Foster
- Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada
| | - Scotty Kupsch
- Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada
| | - Khara Sauro
- Department of Community Health Sciences and O'Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada
| | - Kirsten M Fiest
- Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada
- Department of Community Health Sciences and O'Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada
- Department of Psychiatry & Hotchkiss Brain Institute, University of Calgary, Calgary, Canada
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Boyd A, Kirwan M, Bannon L. Nurses' usage of validated tools to assess for delirium in general acute care settings: A scoping review protocol. HRB Open Res 2025; 8:33. [PMID: 40416446 PMCID: PMC12103707 DOI: 10.12688/hrbopenres.14081.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/11/2025] [Indexed: 05/27/2025] Open
Abstract
Background Delirium is an acute, neuropsychiatric syndrome, characterized by an altered mental state. It often affects hospital in-patients and is associated with an increased risk of mortality, dementia, and functional decline. Delirium can be detected through the use of validated assessment tools, administered by nurses, and early detection is associated with improved outcomes for patients. However, validated tools are infrequently utilised and cases of delirium are frequently missed. A greater understanding of nurses' use of validated delirium assessment tools is needed in order to reduce the number of missed cases. Objectives The aim of this scoping review is to identify how validated assessment tools are used by nurses in general acute care settings to assess for delirium and identify the barriers and enablers for said tools' use. Methods This scoping review will be conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews. The databases CINAHL, PubMed, Web of Science, and Scopus will be searched using a search strategy. Grey literature will also be searched using Google Scholar and BASE. Results will be uploaded to Covidence where the sources will be screened for relevance. Data from relevant sources will be extracted using a data extraction tool. Results The PRISMA-ScR flow diagram will present the results of the search. Results will be mapped descriptively and presented as both tabulated results and a narrative summary. Conclusion This protocol outlines the structure of a scoping review that will analyse the existing literature surrounding nurses use of validated delirium assessment tools. This review aims to map the evidence of delirium assessment tool utilisation by nurses and identify any barriers to usage. This will support future researchers and policy makers in the improvement of delirium assessment in acute care settings.
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Affiliation(s)
- Aoibhinn Boyd
- Dublin City University School of Nursing Psychotherapy and Community Health, Dublin, Leinster, Ireland
| | - Marcia Kirwan
- Dublin City University School of Nursing Psychotherapy and Community Health, Dublin, Leinster, Ireland
| | - Leona Bannon
- Dublin City University School of Nursing Psychotherapy and Community Health, Dublin, Leinster, Ireland
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Butala A, Gilbert JM, Griffiths AA, Lim WK. Impact of hospital readmissions following hospitalisation with delirium on 12-month mortality: a quaternary Australian hospital experience. Eur Geriatr Med 2025; 16:271-280. [PMID: 39543013 DOI: 10.1007/s41999-024-01084-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 10/02/2024] [Indexed: 11/17/2024]
Abstract
PURPOSE Inpatient delirium and unplanned hospital readmissions are associated with increased mortality. This study aimed to determine the effect of 28-day unplanned hospital readmissions on 12-month mortality post-discharge in patients with delirium during index hospitalisation. METHODS Retrospective longitudinal cohort study of adults aged 65 or above with delirium during hospitalisation at a Victorian quaternary hospital was performed. Delirium was identified by the inclusion of ICD-10 (International Classification of Diseases, 10th revision) codes in the hospital medical discharge summary. Descriptive statistics was obtained for baseline characteristics. Cox proportional hazards model was developed to identify independent predictors of 12-month post-discharge mortality. RESULTS One thousand six hundred thirty-four patients with delirium during in-patient admission were included. The overall 12-month mortality rate was 35% (572 patients). Of the 1,425 patients who survived their index admission, 11.2% had an unplanned 28-day readmission. In Cox regression analysis, unplanned readmission (hazard ratio (HR) 2.3, 95% confidence internal (CI) 1.7-2.9), older age (HR 1.38, CI 1.11-1.72), Charlson Comorbidity Index (HR 1.21, CI 1.17-1.27), and discharge to nursing home (HR 1.58, CI 1.23-2.02) were independent predictors of 12-month mortality. Readmitted patients with 12-month mortality were older, with higher rates of dementia, polypharmacy, and nursing home residence compared to readmitted patients who did not reach this endpoint. CONCLUSION Unplanned hospital readmission within 28 days of discharge is an independent predictor of 12-month mortality post in-hospital delirium admission. Admissions complicated by delirium and readmission episodes should instigate discussions regarding prognostication and goals of care. Greater research is required to minimise hospital readmission rates following discharge in this cohort.
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Affiliation(s)
- Anvi Butala
- Department of Geriatrics, Royal Melbourne Hospital, Melbourne, VIC, Australia.
- Department of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia.
| | | | - Alyssa A Griffiths
- Department of Geriatrics, Royal Melbourne Hospital, Melbourne, VIC, Australia
| | - Wen K Lim
- Department of Geriatrics, Royal Melbourne Hospital, Melbourne, VIC, Australia
- Department of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia
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Clark JR, Batra A, Tessier RA, Greathouse K, Dickson D, Ammar A, Hamm B, Rosenthal LJ, Lombardo T, Koralnik IJ, Skolarus LE, Schroedl CJ, Budinger GRS, Wunderink RG, Dematte JE, Ungvari Z, Liotta EM. Impact of healthcare system strain on the implementation of ICU sedation practices and encephalopathy burden during the early COVID-19 pandemic. GeroScience 2025; 47:189-203. [PMID: 39243283 PMCID: PMC11872818 DOI: 10.1007/s11357-024-01336-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 08/31/2024] [Indexed: 09/09/2024] Open
Abstract
The COVID-19 pandemic posed unprecedented challenges to healthcare systems worldwide, particularly in managing critically ill patients requiring mechanical ventilation early in the pandemic. Surging patient volumes strained hospital resources and complicated the implementation of standard-of-care intensive care unit (ICU) practices, including sedation management. The objective of this study was to evaluate the impact of an evidence-based ICU sedation bundle during the early COVID-19 pandemic. The bundle was designed by a multi-disciplinary collaborative to reinforce best clinical practices related to ICU sedation. The bundle was implemented prospectively with retrospective analysis of electronic medical record data. The setting was the ICUs of a single-center tertiary hospital. The patients were the ICU patients requiring mechanical ventilation for confirmed COVID-19 between March and June 2020. A learning health collaborative developed a sedation bundle encouraging goal-directed sedation and use of adjunctive strategies to avoid excessive sedative administration. Implementation strategies included structured in-service training, audit and feedback, and continuous improvement. Sedative utilization and clinical outcomes were compared between patients admitted before and after the sedation bundle implementation. Quasi-experimental interrupted time-series analyses of pre and post intervention sedative utilization, hospital length of stay, and number of days free of delirium, coma, or death in 21 days (as a quantitative measure of encephalopathy burden). The analysis used the time duration between start of the COVID-19 wave and ICU admission to identify a "breakpoint" indicating a change in observed trends. A total of 183 patients (age 59.0 ± 15.9 years) were included, with 83 (45%) admitted before the intervention began. Benzodiazepine utilization increased for patients admitted after the bundle implementation, while agents intended to reduce benzodiazepine use showed no greater utilization. No "breakpoint" was identified to suggest the bundle impacted any endpoint measure. However, increasing time between COVID-19 wave start and ICU admission was associated with fewer delirium, coma, and death-free days (β = - 0.044 [95% CI - 0.085, - 0.003] days/wave day); more days of benzodiazepine infusion (β = 0.056 [95% CI 0.025, 0.088] days/wave day); and a higher maximum benzodiazepine infusion rate (β = 0.079 [95% CI 0.037, 0.120] mg/h/wave day). The evidence-based practice bundle did not significantly alter sedation utilization patterns during the first COVID-19 wave. Sedation practices deteriorated and encephalopathy burden increased over time, highlighting that strategies to reinforce clinical practices may be hindered under conditions of extreme healthcare system strain.
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Affiliation(s)
- Jeffrey R Clark
- Northwestern University-Feinberg School of Medicine, Chicago, IL, USA
- Columbia University Irving Medical Center, New York, NY, USA
| | - Ayush Batra
- Ken & Ruth Davee Department of Neurology, Northwestern University-Feinberg School of Medicine, 625 N. Michigan Ave, Suite 1150, Chicago, IL, 60611, USA
| | - Robert A Tessier
- Northwestern University-Feinberg School of Medicine, Chicago, IL, USA
| | - Kasey Greathouse
- Northwestern University-Feinberg School of Medicine, Chicago, IL, USA
| | - Dan Dickson
- Northwestern University-Feinberg School of Medicine, Chicago, IL, USA
| | - Abeer Ammar
- Northwestern University-Feinberg School of Medicine, Chicago, IL, USA
| | - Brandon Hamm
- Department of Psychiatry and Behavioral Sciences, Northwestern University-Feinberg School of Medicine, Chicago, IL, USA
| | - Lisa J Rosenthal
- Department of Psychiatry and Behavioral Sciences, Northwestern University-Feinberg School of Medicine, Chicago, IL, USA
| | - Theresa Lombardo
- Northwestern University-Feinberg School of Medicine, Chicago, IL, USA
| | - Igor J Koralnik
- Ken & Ruth Davee Department of Neurology, Northwestern University-Feinberg School of Medicine, 625 N. Michigan Ave, Suite 1150, Chicago, IL, 60611, USA
| | - Lesli E Skolarus
- Ken & Ruth Davee Department of Neurology, Northwestern University-Feinberg School of Medicine, 625 N. Michigan Ave, Suite 1150, Chicago, IL, 60611, USA
| | - Clara J Schroedl
- Department of Medicine, Division of Pulmonary and Critical Care, Northwestern University-Feinberg School of Medicine, Chicago, IL, USA
| | - G R Scott Budinger
- Department of Medicine, Division of Pulmonary and Critical Care, Northwestern University-Feinberg School of Medicine, Chicago, IL, USA
| | - Richard G Wunderink
- Department of Medicine, Division of Pulmonary and Critical Care, Northwestern University-Feinberg School of Medicine, Chicago, IL, USA
| | - Jane E Dematte
- Department of Medicine, Division of Pulmonary and Critical Care, Northwestern University-Feinberg School of Medicine, Chicago, IL, USA
| | - Zoltan Ungvari
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral College/Department of Public Health, Semmelweis University, Budapest, Hungary
| | - Eric M Liotta
- Ken & Ruth Davee Department of Neurology, Northwestern University-Feinberg School of Medicine, 625 N. Michigan Ave, Suite 1150, Chicago, IL, 60611, USA.
- International Training Program in Geroscience, Doctoral College/Department of Public Health, Semmelweis University, Budapest, Hungary.
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Qiu L, Ma Y, Ge L, Zhou H, Jia W. Efficacy of Cerebral Oxygen Saturation Monitoring for Perioperative Neurocognitive Disorder in Adult Noncardiac Surgical Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. World Neurosurg 2025; 194:123570. [PMID: 39701521 DOI: 10.1016/j.wneu.2024.123570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/08/2024] [Accepted: 12/08/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND Perioperative neurocognitive disorders are common perioperative complications associated with various poor outcomes. Regional cerebral oxygen saturation (rSO2) monitoring is a noninvasive technique based on near-infrared spectroscopy detection. Due to the considerable controversy among currently published studies on the application of intraoperative rSO2 monitoring in adult patients undergoing elective noncardiac surgery, this study aims to conduct a systematic review and meta-analysis to provide more comprehensive and robust evidence to support clinical decision-making. METHODS This study conducted a systematic literature search of databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science, from their inception to May 1, 2024. The eligible randomized controlled trials included adult patients undergoing elective noncardiac surgery under general anesthesia who received optimized anesthesia management guided by rSO2 monitoring and those in the control group who received routine anesthesia management under standard monitoring or blinded rSO2 monitoring. The primary outcomes were the incidence of perioperative neurocognitive disorders, including postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), and Mini-Mental State Examination (MMSE) scores. Secondary outcomes included the incidence of intraoperative cerebral desaturation and length of hospital stay (LOS). RESULTS The pooled results showed that compared to the control group, optimized anesthesia management guided by intraoperative rSO2 monitoring significantly reduced the incidence of POCD within 7 days postoperatively and may reduce the incidence of POCD at 3 months and longer periods postoperatively. However, it may not reduce the incidence of POD within 7 days or longer periods postoperatively, improve MMSE scores, reduce the incidence of intraoperative cerebral desaturation, or shorten LOS. Given the substantial heterogeneity in the pooled results for MMSE scores within 7 days postoperatively and LOS, and the limited number of studies reporting the incidence of POD, POCD, and MMSE scores after 7 days postoperatively, the related results should be interpreted with caution. CONCLUSIONS Despite the presence of heterogeneity and the inclusion of a limited number of studies for some outcomes, it is still recommended that clinical anesthesiologists routinely perform intraoperative rSO2 monitoring and optimize intraoperative anesthesia management based on the monitoring results to maximize rSO2 and improve cerebral perfusion, thereby improving patients' neurocognitive outcomes. Further large-scale, high-quality studies are needed to confirm the conclusions of this study.
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Affiliation(s)
- Lingqin Qiu
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, Gansu Province, China.
| | - Yabing Ma
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, Gansu Province, China
| | - Li Ge
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, Gansu Province, China
| | - Haijiao Zhou
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, Gansu Province, China
| | - Wenqin Jia
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, Gansu Province, China
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Sakusic A, Rabinstein AA. ICU Delirium. Neurol Clin 2025; 43:1-13. [PMID: 39547734 DOI: 10.1016/j.ncl.2024.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2024]
Abstract
Delirium is not a harmless transient event during ICU hospitalization; rather, it is a severe complication of critical illness associated with increased mortality, morbidity, and persistent disability. Despite being recognized for decades, it remains underdiagnosed. Employing validated tools for detection helps reduce missed cases. Early detection facilitates prompt management. Sedatives, opioids, and antipsychotics should be avoided whenever possible. Optimizing environmental triggers, minimizing iatrogenicity, and treating underlying critical illness constitute the basis of the currently recommended approach to diminish the burden of delirium in ICU patients.
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Affiliation(s)
- Amra Sakusic
- Neurology Department, Mayo Clinic, Jacksonville, FL, USA; Neurology Department, Mayo Clinic Rochester, 200 First Street Southwest, Rochester, MN 55905, USA.
| | - Alejandro A Rabinstein
- Neurology Department, Mayo Clinic Rochester, 200 First Street Southwest, Rochester, MN 55905, USA; 1216 2nd Street Southwest, Rochester, MN 55902, USA
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35
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Denver P, Tortorelli L, Hov K, Berg JP, Giil LM, Nazmi A, Lopez-Rodriguez A, Healy D, Murray C, Barry R, Watne LO, Cunningham C. Chemokine associations with blood cerebrospinal fluid (CSF) barrier permeability and delirium. Brain Behav Immun Health 2025; 43:100920. [PMID: 39839987 PMCID: PMC11750293 DOI: 10.1016/j.bbih.2024.100920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Accepted: 12/01/2024] [Indexed: 01/23/2025] Open
Abstract
Delirium is a highly prevalent neuropsychiatric syndrome characterised by acute and fluctuating impairments in attention and cognition. Mechanisms driving delirium are poorly understood but it has been suggested that blood cytokines and chemokines cross the blood brain barrier during delirium, directly impairing brain function. It is not known whether these molecules reach higher brain levels when the blood cerebrospinal fluid barrier (BCSFB) is impaired. Here, in human hip-fracture patients, we tested the influence of BCSFB integrity on CSF levels of chemokines and assessed their association with delirium. CSF levels of IP-10, eotaxin, eotaxin 3 and TARC showed weak to moderate correlations with BCSFB permeability, as measured by the Qalbumin ratio, while MCP1, IL-8, MIP1α and MIP1β showed no significant correlation. Chemokines were not associated with delirium in univariate analysis or when stratified on dementia status, but exploratory analyses showed that elevated Eotaxin (CCL11) and MIP1α (CCL3) were associated with prevalent delirium. Modelling acute systemic inflammation, we used bacterial LPS (250 μg/kg) or sterile laparotomy surgery in mice to demonstrate de novo synthesis of chemokines at the choroid plexus (CP) and microvasculature. Gene expression data showed CP-enriched expression of Il1b, Tnfa, Cxcl1 and Ccl3 in both models and immunohistochemistry showed cytokine and chemokine synthesis in CP stromal (IL-1β, CCL2/MCP1) or epithelial cells (CXCL10/IP-10) cells and at the microvasculature. Larger studies are required to confirm these human findings on chemokine associations with BCSFB permeability and prevalent delirium. Preclinical studies are warranted to determine whether chemokines might play a role in the pathophysiology of delirium.
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Affiliation(s)
- Paul Denver
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, Ireland
| | - Lucas Tortorelli
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, Ireland
| | - Karen Hov
- Oslo Delirium Research Group, Department of Geriatric Medicine, Akershus University Hospital, Lørenskog, Norway
| | | | - Lasse M. Giil
- Department of Clinical Science, University of Bergen, 5020, Bergen, Norway
| | - Arshed Nazmi
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, Ireland
| | - Ana Lopez-Rodriguez
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, Ireland
| | - Daire Healy
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, Ireland
| | - Carol Murray
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, Ireland
| | - Robyn Barry
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, Ireland
| | - Leiv Otto Watne
- Oslo Delirium Research Group, Department of Geriatric Medicine, Akershus University Hospital, Lørenskog, Norway
- Institute of Clinical Medicine, University of Oslo, Norway
| | - Colm Cunningham
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, Ireland
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Pasqui E, de Donato G, Brancaccio B, Casilli G, Ferrante G, Palasciano G. A novel risk assessment tool for postoperative delirium in vascular surgery: The stress model (Siena posTopeRative dElirium in vaScular Surgery). Vascular 2025; 33:212-222. [PMID: 38419265 DOI: 10.1177/17085381241236926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2024]
Abstract
OBJECTIVE Postoperative delirium (POD) is a common complication with a high health-related impact. The creation of a model (Siena posTopeRative dElirium in vaScular Surgery) to identify high-risk patients with consecutive prompt diagnosis and correct management. METHODS This is an observational retrospective study to evaluate POD incidence in patients who underwent elective vascular surgery procedures between 2018 and 2020. POD was detected using CAM and defined as the onset of an acute confusional state, clinically manifesting as a disturbed state of consciousness, cognitive dysfunction, or alteration in perception and behavior. The total population was divided in the development and validation subsamples. Multivariable logistic regression analysis was performed, identifying variables related to the occurrence of POD. An additive score was created and the STRESS score was internally validated using the Validation subgroup. RESULTS A total of 1067 patients were enrolled. POD occurred in 111 cases (10.4%). Multivariable logistic regression analysis for POD occurrence revealed as significant predictors: age>75 years, CKD, dyslipidaemia, psychiatric disease, CAD, hospitalization in the previous month, preoperative NLR >3.59, preoperative Hb < 12 g/dl, preoperative Barthel score <75, major amputation, CLTI revascularization, general anesthesia, and postoperative urinary catheter. These variables were used to create the STRESS score. The model was applied to both development and validation subgroups; AUC was respectively 0.7079 (p < .0001) and 0.7270 (p < .0001). CONCLUSION The STRESS score has a good predictive potentiality for POD occurrence in elective vascular surgery procedures. However, implementation and external validation are needed to be correctly used in everyday clinical practice.
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Affiliation(s)
- Edoardo Pasqui
- Vascular Surgery Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Gianmarco de Donato
- Vascular Surgery Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Brenda Brancaccio
- Vascular Surgery Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Giulia Casilli
- Vascular Surgery Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Giulia Ferrante
- Vascular Surgery Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Giancarlo Palasciano
- Vascular Surgery Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
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Singh C, Billing HS, Bhupal SS, Kohli I, Sohal A, Roytman M. Delirium due to any cause is associated with higher resource utilization in patients undergoing liver transplantation: analysis of the National Inpatient Sample. Eur J Gastroenterol Hepatol 2025; 37:207-213. [PMID: 39589816 DOI: 10.1097/meg.0000000000002888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2024]
Abstract
OBJECTIVE The only curative treatment for patients with end-stage liver disease (ESLD) is liver transplantation (LT). Patients with ESLD can develop delirium due to multiple etiologies. In this study, we aimed to assess the prevalence and impact of delirium on outcomes and resource utilization among hospitalized patients undergoing LT. METHODS We used the National Inpatient Sample Database 2016-2020 to identify adult patients undergoing LT. Patients were stratified into two groups based on the presence of delirium. The outcomes studied were in-hospital mortality, perioperative adverse events, and resource utilization. Multivariate logistic and linear regression analysis was used to identify the relationship between delirium and outcomes. RESULTS Of 34 405 included patients, 4930 (14.3%) patients had delirium. Patients with delirium had a higher need for renal replacement therapy (31.7% vs. 17.6%, P < 0.001), vasopressor support (16.8% vs. 11.1%, P < 0.001), and mechanical ventilation (34.1% vs. 15.3%, P < 0.001). They also had higher total perioperative complications (77.3% vs. 60.4%, P < 0.001), longer length of stay (34.8 vs. 17. 7, P < 0.001), and total hospitalization charges ($927 200 vs. $565 486 P < 0.001). After multivariable analysis, patients with delirium had higher odds of perioperative complications (adjusted odds ratio: 1.54, 95% confidence interval: 1.24-1.92, P < 0.001) and resource utilization. CONCLUSION Our finding suggests the need for physicians to identify and reverse delirium as soon as possible.
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Affiliation(s)
- Carol Singh
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab
| | - Harbir S Billing
- Department of Internal Medicine, Government Medical College and Hospital, Chandigarh, India
| | - Sahiljot Singh Bhupal
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab
| | - Isha Kohli
- Graduate Program in Public Health, Icahn School of Medicine, Mount Sinai, New York
| | - Aalam Sohal
- Division of Hepatology, Liver Institute Northwest, Seattle, Washington
| | - Marina Roytman
- Division of Gastroenterology and Hepatology, University of California San Francisco, Fresno, California, USA
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Schwab H, Sines B, Moreton E, Palanca BJ, Austin CA. The Association Between Selective Serotonin Reuptake Inhibitors and the Incidence of Delirium in Critically Ill Patients: A Systematic Review. Crit Care Explor 2025; 7:e1217. [PMID: 39964698 PMCID: PMC11838155 DOI: 10.1097/cce.0000000000001217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2025] Open
Abstract
OBJECTIVES To investigate the: 1) correlation between the maintenance or cessation of selective serotonin reuptake inhibitors (SSRIs) during hospitalization and the incidence of delirium among critically ill patients; 2) evaluate the effectiveness of utilizing SSRIs as a potential intervention for managing delirium in critically ill adults; and 3) evaluate the effects of continuing SSRIs in patients who were previously prescribed these medications on incidence of delirium or withdrawal symptoms manifesting as delirium. DATA SOURCES PubMed, Scopus, Embase, PsycInfo, and ProQuest Central, and additional studies identified from reference lists and relevant systematic reviews. STUDY SELECTION Studies included adults 18 years old and older with critical illness necessitating ICU care administered SSRIs during their hospital stay, where delirium and/or adverse effects were reported as outcomes. DATA EXTRACTION Two team members extracted data from included studies into evidence tables, which were subsequently discussed to synthesize and align the extracted findings. Extraction criteria included study population and the type of control or comparison group, exposures, primary and secondary outcome measures, results, and implications. We used Study Quality Assessment Tools provided by the National Heart, Lung, and Blood Institute and National Institutes of Health public websites along with the TREND checklist to evaluate the quality of articles and analyze for bias. DATA SYNTHESIS Two reviewers analyzed the studies' risk for bias. Analysis followed the Grading of Recommendations Assessment, Development, and Evaluation criteria used in Cochrane systematic reviews. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist to design and report the study. CONCLUSIONS The cessation of SSRIs in patients who were previously prescribed these medications is associated with an increased incidence of delirium or withdrawal symptoms manifesting as delirium. Continuing these medications in the setting of critical illness may mitigate the risk of delirium. Further investigation is warranted into the impact of SSRIs on delirium in patients not taking these medications prior to ICU admission.
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Affiliation(s)
- Hailey Schwab
- Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, FL
| | - Benjamin Sines
- Division of Pulmonary and Critical Care Medicine, University of North Carolina, Chapel Hill, NC
| | - Elizabeth Moreton
- Health Sciences Library, University of North Carolina, Chapel Hill, NC
| | - Ben Julian Palanca
- Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO
- Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO
| | - C. Adrian Austin
- Division of Pulmonary and Critical Care Medicine, University of North Carolina, Chapel Hill, NC
- Division of Geriatric Medicine and Center for Aging and Health, University of North Carolina, Chapel Hill, NC
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Lim Z, Ling N, Merchant RA. The interplay of delirium and frailty in hospitalized older adults: Implications for healthcare utilization. J Intern Med 2025; 297:227-229. [PMID: 39673370 DOI: 10.1111/joim.20046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2024]
Affiliation(s)
- Zhiying Lim
- Division of Geriatric Medicine, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Natalie Ling
- Division of Geriatric Medicine, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Reshma Aziz Merchant
- Division of Geriatric Medicine, Department of Medicine, National University Hospital, Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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Xu HB, Shu M, Wu JJ, Li RF, Lin XH, Zhang HG. Impact of delirium on post-discharge mortality in coronary care unit patients: A retrospective cohort study. Nurs Crit Care 2025. [PMID: 39854133 DOI: 10.1111/nicc.13240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 10/31/2024] [Accepted: 12/05/2024] [Indexed: 01/26/2025]
Abstract
BACKGROUND Coronary care unit (CCU) patients surviving to discharge still face significant mortality. Delirium is common in CCU patients and has been associated with poorer CCU and in-hospital outcomes. AIM To assess the association between delirium and mortality after hospital discharge in CCU survivors. STUDY DESIGN This was a retrospective observational study that included patients admitted to CCU. All data were extracted from the Medical Information Mart for Intensive Care IV database. The exposure was delirium during CCU stay. The primary outcome was mortality 180 days after hospital discharge. Secondary outcomes included post-hospital discharge mortality at 90 days, length of CCU and hospital stays, and hospital discharge disposition. RESULTS Of the 3609 CCU patients included, 891 were considered delirium-positive during their CCU stay. Delirium was associated with an increased risk of mortality at 180 days after hospital discharge (adjusted hazard ratio [HR], 1.33; 95% confidence interval (CI), 1.08-1.64). Similar results were observed for 90-day post-discharge mortality (adjusted HR,1.43; 95% CI, 1.13-1.83). CCU patients who experienced delirium had longer stays in both the CCU and hospital (adjusted β, 2.11; 95% CI, 1.79-2.43 and 3.87; 95% CI, 3.06-4.69, respectively). They were also more likely to require nursing care after hospital discharge (adjusted odds ratio [OR], 1.65; 95% CI, 1.22-2.22). CONCLUSION Delirium during CCU stay was associated with an increased risk of all-cause mortality up to 180 days in CCU patients who survived hospital discharge. RELEVANCE TO CLINICAL PRACTICE Delirium places CCU patients at a higher risk of post-discharge mortality and increased health care resource requirements. Given the high prevalence of delirium in CCU patients and its significantly deleterious impact on both short-term and long-term post-discharge mortality, nurses and physicians should enhance the post-discharge management of patients who experience delirium in order to improve prognosis. This also highlights the importance of preventing and managing delirium during hospitalization.
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Affiliation(s)
- Hong-Bo Xu
- Department of Critical Care Medicine, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
| | - Min Shu
- Department of Emergency Medicine, Shenzhen Nanshan People's Hospital, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
| | - Jia-Jun Wu
- Department of Emergency Medicine, Shenzhen Nanshan People's Hospital, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
| | - Rui-Fa Li
- Department of Critical Care Medicine, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
| | - Xiao-Hua Lin
- Department of Critical Care Medicine, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
| | - Hai-Gang Zhang
- Department of Critical Care Medicine, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
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Manfredini L, Pépin M, Ayar PV, Gay M, Certin M, Ayar PV. The association of biological sex and long-term outcomes in older patients with physical restraint at the emergency department. BMC Geriatr 2025; 25:30. [PMID: 39810080 PMCID: PMC11731348 DOI: 10.1186/s12877-025-05689-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 01/07/2025] [Indexed: 01/16/2025] Open
Abstract
BACKGROUND The worldwide population is ageing and self-arm can be prevented with many techniques. Among them coercive measure consisting of physical restraint (PR) is one of the techniques. This study aims to assess the effects of the biological sex on the long-term survival after PR in geriatric patients during the initial emergency department (ED) visit. METHODS This retrospective study included patients between November 2019 to March 2021. All consecutive hospitalized patients after emergency department visit older than 75 years with PR were included. The population was compared according to the biological sex. One-year all-cause mortality was plotted with the Kaplan-Meier curve. Hazard ratios (HRs) for 1-year mortality were calculated using a Cox proportional hazards regression model. Mortality was monitored over a 3-year period. RESULTS PR was used in 149 patients representing 4.6% of 3210 hospitalized patients older than 75 years after ED visit. Women represented 52% of the study population. Compared to men, women were older [median (IQR) age 89 (85-93) vs. 85 (81-90) years, P = 0.002]. Women more often presented dementia (93 vs. 80%, P = 0.031). Both sexes presented the same limited independence. All-cause mortality was significantly lower for women than men after one year (25 vs. 51%, respectively, P = < 0.001). Likewise, adjusted HR of 1-year all-cause mortality was higher in men [a HR 3.4 (95% confidence interval 1.7-7.1), P < 0.001]. CONCLUSION This study suggested that the use of physical restraint in older adults was a more related factor of mortality in men than women. Women were older with lower expectancy life but PR use seemed to be a sign of global health decline in men. Further prospective studies are needed to assess if mortality after PR use is a cause or a consequence of a global health decline.
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Affiliation(s)
| | - Marion Pépin
- Geriatrics, APHP, UVSQ, Hopital Ambroise-Pare, Boulogne-Billancourt, France
- Clinical Epidemiology, CESP, INSERM, Paris Saclay University, Villejuif, France
| | - Pradeebane Vaittinada Ayar
- Laboratoire des Sciences du Climat et l'Environnement (LSCE-IPSL), CNRS/CEA/UVSQ, Université Paris-Saclay, Gif-sur-Yvette, UMR8212, 91190, France
| | - Matthieu Gay
- Emergency Department, Beaujon Hospital AP-HP, Clichy, France
| | - Marie Certin
- Emergency Department, Beaujon Hospital AP-HP, Clichy, France
| | - Prabakar Vaittinada Ayar
- Emergency Department, Beaujon Hospital AP-HP, Clichy, France.
- INSERM UMR-S942, MASCOTT, Paris, France.
- University of Paris Cité, Paris, France.
- Emergency Department, 100, Boulevard du Général Leclerc, Clichy, 92300, France.
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Jiang S, Gunther M. A Critical Reappraisal of Haloperidol for Delirium Management in the Intensive Care Unit: Perspective from Psychiatry. J Clin Med 2025; 14:438. [PMID: 39860443 PMCID: PMC11766117 DOI: 10.3390/jcm14020438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 01/02/2025] [Accepted: 01/08/2025] [Indexed: 01/27/2025] Open
Abstract
Delirium is a complex neuropsychiatric syndrome with multifactorial pathophysiology, encompassing a wide range of neuropsychiatric symptoms, and its management remains a significant challenge in critical care. Although often managed with antipsychotics, like haloperidol, current research has predominantly focused on dopamine dysregulation as the primary driver of delirium, overlooking its broader neuroanatomical and neurochemical underpinnings. This has led to a majority of research focusing on haloperidol as a treatment for intensive care unit (ICU) delirium. Our review critically evaluates the role of haloperidol in ICU delirium management, particularly in light of recent large-scale randomized controlled trials (RCTs) that have primarily focused on delirium-free days and mortality as the primary endpoints. These studies highlight an limited understanding of the true nature of delirium treatment, which requires a broader, neuropsychiatric approach. We argue that future research should shift focus to neuropsychiatric symptoms such as agitation and psychosis and explore the clinical and functional benefits of reducing these distressing symptoms. Additionally, the stratification of delirium by subtypes and etiology, the enhancement of detection tools, and the adoption of multi-intervention and multi-disciplinary care approaches should be prioritized. Despite the methodological flaws in these studies, the findings support the safety of haloperidol in the ICU setting, with minimal risk of adverse events, particularly cardiac and neuropsychiatric. Moving forward, delirium research must integrate modern neuroscientific understanding and adopt more multi-disciplinary input and nuanced, patient-centered approaches to truly advance clinical care and outcomes.
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Affiliation(s)
- Shixie Jiang
- Department of Psychiatry, University of Florida College of Medicine, Gainesville, FL 32608, USA
| | - Matthew Gunther
- Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Stanford, CA 94305, USA;
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Goodnough CL, Montoya J, Cartusciello EB, Floranda EL, Gross ER. Nicotinamide adenine dinucleotide supplementation fails to enhance anesthetic recovery in rodents. Sci Rep 2025; 15:1428. [PMID: 39789056 PMCID: PMC11718248 DOI: 10.1038/s41598-024-83500-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Accepted: 12/16/2024] [Indexed: 01/12/2025] Open
Abstract
Nicotinamide Adenine Dinucleotide (NAD+) is implicated in bioenergetics, DNA repair, and senescence. Depletion of NAD+ is associated with aging and neurodegenerative disease, prompting a growing interest in NAD+ supplementation. With rising over-the-counter use of NAD, understanding their impact on anesthetic recovery becomes essential. This study investigates the effect of NADH, a common NAD+ precursor, on anesthesia in rodents. Baseline and post-anesthesia (1.5% isoflurane) open field and Y-maze activity were recorded in adult male and female C57BL/6 mice (n = 8-10/group). NADH (150 mg/kg, intraperitoneal) or vehicle (0.9% normal saline) were given at baseline or during anesthesia. The NADH-treated group exhibited a significant decrease in open-field activity relative to vehicle-treated. This diminished activity was reflected in reduced distance travelled and average velocity after emergence from anesthesia in the NADH-treated group. NADH treatment did not improve Y-maze performance after anesthesia, partly related to reduced locomotor activity in the NADH-treated group. This study demonstrates that NADH does not appear to hasten recovery from anesthesia. Instead, there was a depression in open-field activity and no change in Y-maze performance with NADH supplementation, indicators of locomotive and cognitive recovery in rodents. The broad implications of NAD+ in aging are likely to shape supplementation trends, highlighting the importance of understanding the potential influence of administering NAD+ on anesthetic sensitivity and recovery.
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Affiliation(s)
- Candida L Goodnough
- Department of Anesthesiology, Perioperative, and Pain Medicine, School of Medicine, Stanford University, Stanford, USA.
| | - July Montoya
- Department of Anesthesiology, Perioperative, and Pain Medicine, School of Medicine, Stanford University, Stanford, USA
| | - Erica B Cartusciello
- Department of Anesthesiology, Perioperative, and Pain Medicine, School of Medicine, Stanford University, Stanford, USA
| | - Erin L Floranda
- Department of Anesthesiology, Perioperative, and Pain Medicine, School of Medicine, Stanford University, Stanford, USA
| | - Eric R Gross
- Department of Anesthesiology, Perioperative, and Pain Medicine, School of Medicine, Stanford University, Stanford, USA
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Holler E, Ludema C, Ben Miled Z, Rosenberg M, Kalbaugh C, Boustani M, Mohanty S. Development and Validation of a Routine Electronic Health Record-Based Delirium Prediction Model for Surgical Patients Without Dementia: Retrospective Case-Control Study. JMIR Perioper Med 2025; 8:e59422. [PMID: 39786865 PMCID: PMC11757977 DOI: 10.2196/59422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 10/15/2024] [Accepted: 11/01/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Postoperative delirium (POD) is a common complication after major surgery and is associated with poor outcomes in older adults. Early identification of patients at high risk of POD can enable targeted prevention efforts. However, existing POD prediction models require inpatient data collected during the hospital stay, which delays predictions and limits scalability. OBJECTIVE This study aimed to develop and externally validate a machine learning-based prediction model for POD using routine electronic health record (EHR) data. METHODS We identified all surgical encounters from 2014 to 2021 for patients aged 50 years and older who underwent an operation requiring general anesthesia, with a length of stay of at least 1 day at 3 Indiana hospitals. Patients with preexisting dementia or mild cognitive impairment were excluded. POD was identified using Confusion Assessment Method records and delirium International Classification of Diseases (ICD) codes. Controls without delirium or nurse-documented confusion were matched to cases by age, sex, race, and year of admission. We trained logistic regression, random forest, extreme gradient boosting (XGB), and neural network models to predict POD using 143 features derived from routine EHR data available at the time of hospital admission. Separate models were developed for each hospital using surveillance periods of 3 months, 6 months, and 1 year before admission. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC). Each model was internally validated using holdout data and externally validated using data from the other 2 hospitals. Calibration was assessed using calibration curves. RESULTS The study cohort included 7167 delirium cases and 7167 matched controls. XGB outperformed all other classifiers. AUROCs were highest for XGB models trained on 12 months of preadmission data. The best-performing XGB model achieved a mean AUROC of 0.79 (SD 0.01) on the holdout set, which decreased to 0.69-0.74 (SD 0.02) when externally validated on data from other hospitals. CONCLUSIONS Our routine EHR-based POD prediction models demonstrated good predictive ability using a limited set of preadmission and surgical variables, though their generalizability was limited. The proposed models could be used as a scalable, automated screening tool to identify patients at high risk of POD at the time of hospital admission.
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Affiliation(s)
- Emma Holler
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Christina Ludema
- Department of Epidemiology & Biostatistics, Indiana University Bloomington, Bloomington, United States
| | - Zina Ben Miled
- Department of Electrical & Computer Engineering, Lamar University, Beaumont, TX, United States
| | - Molly Rosenberg
- Department of Epidemiology & Biostatistics, Indiana University Bloomington, Bloomington, United States
| | - Corey Kalbaugh
- Department of Epidemiology & Biostatistics, Indiana University Bloomington, Bloomington, United States
| | - Malaz Boustani
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Sanjay Mohanty
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, United States
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Liu TH, Lin YT, Wu JY, Huang PY, Tsai WW, Lai CC, Kao PH, Su KP. Pharmacologic prophylaxis of postoperative delirium in elderly patients: A network meta-analysis of randomized controlled trials. J Psychiatr Res 2025; 181:169-178. [PMID: 39615080 DOI: 10.1016/j.jpsychires.2024.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 09/28/2024] [Accepted: 11/03/2024] [Indexed: 01/22/2025]
Abstract
BACKGROUND The high incidence and mortality rates of postoperative delirium (POD) among elderly patients highlights the pressing need for tailored prophylactic strategies. Despite various pharmacologic prophylactic strategies have been reported effective, their overall benefit and safety remain unclear in the geriatric population. Our network meta-analysis (NMA) aimed to systematically evaluate and rank the effectiveness of various pharmacological interventions in preventing POD in elderly patients. METHODS We conducted an extensive search of PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and Google Scholar for randomized controlled trials (RCTs) published up to August 1, 2023. We included RCTs examining pharmacological prophylactic effects of POD in elderly patients. To extract data in alignment with predefined areas of interest, we employed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The primary outcome was the incidence of POD. For secondary outcomes, we evaluated tolerability through all-cause discontinuation or drop-out rates, as well as all-cause mortality. RESULTS Our analysis encompassed a total of 44 RCTs involving 11,178 patients. Out of these, 26 RCTs involved comparisons with placebo only. For delirium prevention, the treatment groups receiving atypical antipsychotics (odds ratio (OR) of 0.27 and 95% confidence interval (CI) of 0.12-0.58), haloperidol (OR of 0.42; 95% CI of 0.25-0.71), dexmedetomidine (OR of 0.51 and 95% CI of 0.37-0.71 and melatonergic agents (MMA) (OR of 0.57 and 95% CI of 0.33-0.98) had significantly lower rates of delirium compared to the placebo group. Notably, the atypical antipsychotics ranked as the most effective treatment. For tolerability, no statistically differences in rates of dropout discontinuation and all-cause mortality among groups allocated to the placebo or individual pharmacological treatments. CONCLUSIONS Based on indirect evidence, our network meta-analysis identified atypical antipsychotics, dexmedetomidine, MMA, and haloperidol as effective in preventing POD in the elderly, with atypical antipsychotics ranking highest. However, it is essential to note that these findings should be confirmed through further RCTs.
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Affiliation(s)
- Ting-Hui Liu
- Department of Psychiatry, Chi Mei Medical Center, Tainan City, Taiwan
| | - Yen-Ting Lin
- Department of General Internal Medicine, Chi Mei Medical Center, Tainan City, Taiwan
| | - Jheng-Yan Wu
- Department of Nutrition, Chi Mei Medical Center, Tainan City, Taiwan
| | - Po-Yu Huang
- Department of Internal Medicine, Chi Mei Medical Center, Tainan City, Taiwan
| | - Wen-Wen Tsai
- Department of Neurology, Chi Mei Medical Center, Tainan City, Taiwan
| | - Chih-Cheng Lai
- Department of Internal Medicine, Chi Mei Medical Center, Tainan City, Taiwan
| | - Pei-Hsin Kao
- Department of Psychiatry, Chi Mei Medical Center, Tainan City, Taiwan.
| | - Kuan-Pin Su
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan; An-Nan Hospital, China Medical University, Tainan, Taiwan.
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46
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Jia B, Zhou S, Li J, Wan L, Zhou Y, Cui Y. Risk of drug-induced delirium in older patients- a pharmacovigilance study of FDA adverse event reporting system database. Expert Opin Drug Saf 2025; 24:79-87. [PMID: 38755113 DOI: 10.1080/14740338.2024.2357242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 03/28/2024] [Indexed: 05/18/2024]
Abstract
BACKGROUND Drug-induced delirium is known risk factors associated with increased morbidity and mortality in older patients. The objective was to evaluate the risk of drug-related delirium in older patients based on the FDA Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS Delirium reports in older patients (age ≥65) extracted from the FAERS database using Open Vigil 2.1. The reported odds ratio and the proportional reported ratio were calculated to detect the adverse reaction signal of delirium. Combined with published evidence, suspected drugs were categorized as known, possible, or new potential delirium-risk-increasing drugs. RESULTS Of the 130,885 reports (including 28,850 delirium events and 1,857 drugs) analyzed for this study, 314 positive signal drugs were detected. Positive signal drugs are mainly concentrated on the drug of nervous system, cardiovascular system , alimentary tract and metabolism and anti-infectives for systemic use. Of the positive signal drugs, 26.11% (82/314) were known delirium-risk increasing drugs, 44.90% (141/314) were possible and 28.98% (91/314) were new potential. CONCLUSION Drug-induced delirium risk is prevalent in older patients, according to the FAERS. The risk level of drug-induced delirium should be taken into account to optimize drug therapy in clinical practice.
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Affiliation(s)
- Boying Jia
- Department of Pharmacy, Peking University First Hospital, Beijing, China
- Department of Pharmacy, The First Hospital of Tsinghua University, Beijing, China
| | - Shuang Zhou
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Jiayu Li
- Department of Pharmacy, Peking University First Hospital, Beijing, China
- Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Liyan Wan
- Department of Pharmacy, The First Hospital of Tsinghua University, Beijing, China
| | - Ying Zhou
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Yimin Cui
- Department of Pharmacy, Peking University First Hospital, Beijing, China
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Devlin JW, Sieber F, Akeju O, Khan BA, MacLullich AMJ, Marcantonio ER, Oh ES, Agar MR, Avelino-Silva TJ, Berger M, Burry L, Colantuoni EA, Evered LA, Girard TD, Han JH, Hosie A, Hughes C, Jones RN, Pandharipande PP, Subramanian B, Travison TG, van den Boogaard M, Inouye SK. Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS). Crit Care Med 2025; 53:e15-e28. [PMID: 39774202 DOI: 10.1097/ccm.0000000000006514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
OBJECTIVES To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults. DESIGN A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs). METHODS To provide background and context, a review of delirium treatment randomized controlled trials (RCTs) published between 2003 and 2023 was conducted and evidence gaps were identified. The four panels addressed the identified subtopics. For each subtopic, research challenges were identified and recommendations to address each were proposed through virtual discussion before a live, full-day, and in-person conference. General agreement was reached for each proposed recommendation across the entire working group via moderated conference discussion. Recommendations were synthesized across panels and iteratively discussed through rounds of virtual meetings and draft reviews. RESULTS We identified key evidence gaps through a systematic literature review, yielding 43 RCTs of delirium treatments. From this review, eight unique challenges for delirium treatment trials were identified, and recommendations to address each were made based on panel input. The recommendations start with design of interventions that consider the multifactorial nature of delirium, include both pharmacological and nonpharmacologic approaches, and target pathophysiologic pathways where possible. Selecting appropriate at-risk patients with moderate vulnerability to delirium may maximize effectiveness. Targeting patients with at least moderate delirium severity and duration will include those most likely to experience adverse outcomes. Delirium severity should be the primary outcome of choice; measurement of short- and long-term clinical outcomes will maximize clinical relevance. Finally, plans for handling informative censoring and missing data are key. CONCLUSIONS By addressing key delirium treatment challenges and research gaps, our recommendations may serve as a roadmap for advancing delirium treatment research in older adults.
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Affiliation(s)
- John W Devlin
- Department of Pharmacy and Health Systems Sciences, Bouve College of Health Sciences, Northeastern University, Boston, MA
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA
- Harvard Medical School, Boston, MA
| | - Frederick Sieber
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD
| | - Oluwaseun Akeju
- Harvard Medical School, Boston, MA
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA
- McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA
| | - Babar A Khan
- Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN
- Indiana University Center for Aging Research, Regenstrief Institute, Indianapolis, IN
- Indiana University Center of Health Innovation and Implementation Science, Indianapolis, IN
| | - Alasdair M J MacLullich
- Edinburgh Delirium Research Group, Ageing and Health, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Edward R Marcantonio
- Harvard Medical School, Boston, MA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - Esther S Oh
- Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, Johns Hopkins School of Medicine, Baltimore, MD
- Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD
| | - Meera R Agar
- IMPACCT (Improving Palliative, Aged and Chronic Care through Research and Translation), University of Technology Sydney, Sydney, NSW, Australia
| | - Thiago J Avelino-Silva
- Faculty of Medicine, University of San Paulo, San Paulo, Brazil
- Division of Geriatric Medicine, University of California San Franciso, San Franciso, CA
| | - Miles Berger
- Department of Anesthesiology, School of Medicine, Duke University, Durham, NC
- Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC
- Center for Cognitive Neuroscience, Duke University, Durham, NC
- Alzheimer's Disease Research Center, Duke University, Durham, NC
| | - Lisa Burry
- Departments of Pharmacy and Medicine, Sinai Health System, University of Toronto, Toronto, ON, Canada
- Leslie Dan Faculty of Pharmacy and Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Elizabeth A Colantuoni
- Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
| | - Lis A Evered
- Faculty of Medicine, University of San Paulo, San Paulo, Brazil
- Department of Anesthesiology, Weill Cornell Medicine, New York, NY
- Department of Anaesthesia and Acute Pain Medicine, St. Vincent's Hospital, Melbourne, VIC, Australia
| | - Timothy D Girard
- Center for Research, Investigation, and Systems Modeling of Acute Illness (CRISMA), Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Jin H Han
- Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN
- Geriatric Research, Education, and Clinical Center, Tennessee Valley Healthcare System, Nashville, TN
| | - Annmarie Hosie
- IMPACCT (Improving Palliative, Aged and Chronic Care through Research and Translation), University of Technology Sydney, Sydney, NSW, Australia
- School of Nursing & Midwifery, University of Notre Dame Australia, Sydney, NSW, Australia
- Cunningham Centre for Palliative Care, St Vincent's Health Network, Sydney, NSW, Australia
| | - Christopher Hughes
- Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN
- Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN
| | - Richard N Jones
- Department of Psychiatry and Human Behavior, Department of Neurology, Warren Alpert Medical School, Brown University, Providence, RI
| | - Pratik P Pandharipande
- Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN
- Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN
| | - Balachundhar Subramanian
- Harvard Medical School, Boston, MA
- Department of Anesthesiology, Beth Israel Deaconess Hospital, Boston, MA
| | - Thomas G Travison
- Harvard Medical School, Boston, MA
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA
| | - Mark van den Boogaard
- Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Sharon K Inouye
- Harvard Medical School, Boston, MA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA
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Khaled M, Sabac D, Fuda M, Koubaesh C, Gallab J, Qu M, Lo Bianco G, Shanthanna H, Paul J, Thabane L, Marcucci M. Postoperative pain and neurocognitive outcomes after noncardiac surgery: a systematic review and dose-response meta-analysis. Br J Anaesth 2025; 134:89-101. [PMID: 39393998 DOI: 10.1016/j.bja.2024.08.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 07/20/2024] [Accepted: 08/05/2024] [Indexed: 10/13/2024] Open
Abstract
BACKGROUND Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common after noncardiac surgery. Postsurgical pain is frequent and can persist as chronic postsurgical pain (CPSP). The association between postsurgical pain and POD or POCD is biologically plausible. We conducted this systematic review to evaluate the association between acute postsurgical pain or CPSP and POD or POCD in adults undergoing noncardiac surgery. METHODS We followed Preferred Reporting Items for Systematic Review and Meta-Analyses. We searched MEDLINE, EMBASE, Cochrane, CINAHL and PSYCHINFO up to May 2023. We included cohort, case-control, and cross-sectional studies of any language. Pairs of reviewers independently screened studies, extracted data and assessed the risk of bias using the CLARITY tool and the Joanna Briggs Institute checklist. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Where possible, we conducted random-effects meta-analyses to summarise our findings. RESULTS We analysed 30 studies (>9000 participants) that assessed the association between acute postoperative pain and POD/POCD. Dose-response meta-analyses found that postoperative pain intensity was associated with occurrence of POD (adjusted relative risk [aRR]/unit of pain intensity: 1.26; 95% confidence interval [CI]: 1.17-1.35; low certainty of evidence) and risk of developing POD (aRR/unit of pain intensity: 1.18; 95% CI: 1.08-1.30; low certainty of evidence). There was very low certainty of evidence regarding the association between postoperative pain and POCD. No studies assessed the association between CPSP and POCD. Residual confounding and substantial methodological variability between studies prevented pooling data from many of the included studies and lowered certainty of evidence. CONCLUSIONS Dose-response meta-analyses found that postoperative pain intensity was associated with occurrence of and risk of developing POD. SYSTEMATIC REVIEW PROTOCOL PROSPERO-CRD42021192105.
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Affiliation(s)
- Maram Khaled
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; Perioperative and Surgery Research Program, Population Health Research Institute, David Braley Research Institute, Hamilton, ON, Canada
| | - Denise Sabac
- Department of Health Sciences, McMaster University, Hamilton, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Matthew Fuda
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
| | - Chantal Koubaesh
- School of Medical Education, Newcastle University, Newcastle upon Tyne, UK
| | - Joseph Gallab
- Department of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Marianna Qu
- Department of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Giuliana Lo Bianco
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Harsha Shanthanna
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; Department of Anesthesia, McMaster University, Hamilton, ON, Canada
| | - James Paul
- Department of Anesthesia, McMaster University, Hamilton, ON, Canada
| | - Lehana Thabane
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada
| | - Maura Marcucci
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; Perioperative and Surgery Research Program, Population Health Research Institute, David Braley Research Institute, Hamilton, ON, Canada; Clinical Epidemiology and Research Centre (CERC), Department of Biomedical Sciences, Humanitas University & IRCCS Humanitas Research Hospital, Milan, Italy.
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49
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Vlisides PE, Runstadler N, Martinez S, Ragheb JW, Mentz G, Leis A, Schoettinger A, Hickey K, McKinney A, Brooks J, Zierau M, Norcott A, Mody L, Inouye SK, Avidan MS, Min L. Feasibility of Alerting Systems and Family Care Partner Support for Postoperative Delirium Prevention. J Neurosurg Anesthesiol 2024:00008506-990000000-00136. [PMID: 39696755 DOI: 10.1097/ana.0000000000001016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 11/20/2024] [Indexed: 12/20/2024]
Abstract
BACKGROUND The objective of this study was to determine whether postoperative pager alerts to the Hospital Elder Life Program (HELP), a delirium prevention service, would accelerate program enrollment for older surgical patients. This study also tested feasibility of family care partner interventions for delirium prevention. METHODS This single-center, pilot clinical trial factorially randomized 57 non-cardiac surgical patients ≥70 years of age to 4 arms: (1) standard care, (2) pager alerts to accelerate HELP enrollment, (3) family care partner-based delirium prevention interventions, or (4) a combined arm with both HELP and family interventions. The primary clinical outcome was delirium (assessed through the Confusion Assessment Method). RESULTS In the pager alerting arms, 13/24 (54%) participants were enrolled by HELP on postoperative day 1 compared with 0/26 (0%, P<0.001) in the non-alerting arms. Median [interquartile range] time spent in delirium prevention protocols was significantly longer in pager alerting arms than in non-alerting arms (39 [5 to 75] min vs. 0 [0 to 0] min; P<0.001). Family care partners spent 18 [11 to 25)] hours at the bedside over the first 3 postoperative days. There was no significant difference in delirium occurrence in participants randomized to pager alert arms compared with non-alerting arms (odds ratio, 1.02, 95% CI, 0.97-1.07; P=0.390). Similarly, there was no significant difference in delirium occurrence in family intervention arms compared with nonintervention arms (odds ratio, 0.97; 95% CI 0.93-10.02; P=0.270). CONCLUSIONS Pager alerts significantly reduced time to HELP enrollment, albeit without reducing delirium incidence in this pilot study. Family care partners spent substantial time at the bedside during the study period.
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Affiliation(s)
- Phillip E Vlisides
- Department of Anesthesiology, Michigan Medicine, Ann Arbor, MI
- Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI
| | | | - Selena Martinez
- Department of Anesthesiology, Michigan Medicine, Ann Arbor, MI
| | - Jacqueline W Ragheb
- Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL
| | - Graciela Mentz
- Department of Anesthesiology, Michigan Medicine, Ann Arbor, MI
| | - Aleda Leis
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI
| | | | | | - Amy McKinney
- Department of Anesthesiology, Michigan Medicine, Ann Arbor, MI
| | - Joseph Brooks
- Department of Orthopaedic Surgery, Michigan Medicine, Ann Arbor, MI
| | - Mackenzie Zierau
- College of Health Professions, University of Detroit Mercy, Detroit, MI
| | - Alexandra Norcott
- Department of Internal Medicine, Division of Geriatric and Palliative Medicine, Michigan Medicine, Ann Arbor, MI
- Department of Internal Medicine, Division of Geriatric and Palliative Medicine, Michigan Medicine, Ann Arbor, MI
| | - Lona Mody
- Department of Internal Medicine, Division of Geriatric and Palliative Medicine, Michigan Medicine, Ann Arbor, MI
| | - Sharon K Inouye
- Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Michael S Avidan
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO
| | - Lillian Min
- Department of Internal Medicine, Division of Geriatric and Palliative Medicine, Michigan Medicine, Ann Arbor, MI
- Geriatric Research Education and Clinical Care, Veterans Affairs Arbor Healthcare System, Ann Arbor, MI
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50
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Bratseth V, Watne LO, Neerland BE, Halaas NB, Pollmann CT, Karabeg A, Odegaard OT, Sydnes K, Zetterberg H, Seljeflot I, Helseth R. Increased cell-free DNA in CSF and serum of hip fracture patients with delirium. Brain Commun 2024; 7:fcae452. [PMID: 39737468 PMCID: PMC11683831 DOI: 10.1093/braincomms/fcae452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 11/05/2024] [Accepted: 12/16/2024] [Indexed: 01/01/2025] Open
Abstract
Delirium is a neuropsychiatric syndrome commonly presenting during acute illness. The pathophysiology of delirium is unknown, but neuroinflammation is suggested to play a role. In this cross-sectional study, we aimed to investigate whether cell-free DNA and markers of neutrophil extracellular traps in serum and CSF were associated with delirium and neuronal damage, assessed by neurofilament light chain. Hip fracture patients (n = 491) with a median (25, 75 percentiles) age of 83 (74, 88) years and 69% females were enrolled at Oslo University Hospital, Diakonhjemmet Hospital, Akershus University Hospital and Bærum Hospital. Delirium was assessed daily, pre- and postoperatively. Cognitively healthy adults (n = 32) with a median (25, 75 percentiles) age of 75 (70, 77) years and 53% females were included as controls. Cell-free DNA was measured by using the fluorescent nucleic acid stain Quant-iT PicoGreen® in serum and CSF. Myeloperoxidase-DNA and citrullinated histone H3 were analysed by enzyme-linked immunosorbent assay in serum. Hip fracture patients have significantly higher levels of cell-free DNA and neutrophil extracellular traps in blood than cognitively healthy controls. In hip fracture patients without dementia, cell-free DNA in CSF and serum was significantly higher in patients with (n = 68) versus without (n = 221) delirium after adjusting for age and sex (70 (59, 84) versus 62 (53, 77) ng/ml, P = 0.037) and 601 (504, 684) versus 508 (458, 572) ng/ml, P = 0.007, respectively). In the total hip fracture cohort, CSF levels of cell-free DNA and neurofilament light chain were significantly correlated after adjusting for age and sex (r = 0.441, P < 0.001). The correlation was stronger in those with delirium (r = 0.468, P < 0.001) and strongest in delirious patients without dementia (r = 0.765, P = 0.045). In delirious patients without dementia, significantly higher levels of cell-free DNA in CSF and serum were shown. The association between cell-free DNA and neurofilament light chain suggest simultaneous release of cell-free DNA and neuronal damage during delirium.
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Affiliation(s)
- Vibeke Bratseth
- Oslo Center for Clinical Heart Research, Department of Cardiology Ullevaal, Oslo University Hospital, Oslo 0424, Norway
| | - Leiv Otto Watne
- Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo 0424, Norway
- Department of Geriatric Medicine, Akershus University Hospital, Lørenskog 1478, Norway
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo 0318, Norway
| | - Bjørn Erik Neerland
- Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo 0424, Norway
| | - Nathalie Bodd Halaas
- Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo 0424, Norway
| | | | - Adi Karabeg
- Department of Orthopedic Surgery, Akershus University Hospital, Kongsvinger 2381, Norway
| | - Olav Tobias Odegaard
- Department of Anesthesiology, Akershus University Hospital, Kongsvinger 2381, Norway
| | - Kristian Sydnes
- Department of Orthopedic Surgery, Diakonhjemmet Hospital, Oslo 0319, Norway
| | - Henrik Zetterberg
- Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Mölndal 40530, Sweden
- Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal 40530, Sweden
- Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1H9BT, UK
- UK Dementia Research Institute at UCL, London WC1H9BT, UK
- Hong Center for Neurodegenerative Diseases, Hong Kong HKG, China
- Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53707, USA
| | - Ingebjørg Seljeflot
- Oslo Center for Clinical Heart Research, Department of Cardiology Ullevaal, Oslo University Hospital, Oslo 0424, Norway
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo 0318, Norway
| | - Ragnhild Helseth
- Oslo Center for Clinical Heart Research, Department of Cardiology Ullevaal, Oslo University Hospital, Oslo 0424, Norway
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo 0318, Norway
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