Delirium as an acute brain injury in hospital inpatients: can clinical features and biomarkers predict outcomes?

谵妄是一种急性发作的严重神经精神综合征，每8例住院患者中就有1例受到影响。谵妄与较高的死亡率、新的长期认知障碍和现有神经变性的恶化有关。然而，谵妄的机制仍然知之甚少。一些研究表明其与炎症有关，经常观察到脑脊液和炎症生物标志物升高。近年来，新的临床工具如4AT和NEWS2被开发出来，以提高谵妄的识别和确定。随着机器学习和人工智能的应用，使用常规数据来评估谵妄的风险和结果的情况也在增加。这些发展使得新的研究能够以前所未有的规模解决常规数据编码的谵妄与其他临床变量（如炎症标志物和生理测量）之间的关系。在博士研究项目中我的目标是：1)通过系统综述探索医疗出院总结中报告的谵妄编码的频率和代表性2)使用电子健康记录进行研究，检查谵妄的风险和相关结果，这些电子健康记录使用谵妄评估工具（例如NEWS2和4AT） o风险因素包括炎症（通过临床生物标志物），异常生理参数（如低血压和缺氧）和脑萎缩加剧。结果包括30天死亡率、住院时间、再入院、痴呆（或新的认知障碍）的发展和功能下降。参考文献：Davis D. H., Muniz-Terrera G., Keage H. A., Stephan B. C., Fleming J., Ince P. G., Matthews F. E., Cunningham C., Ely E. W., MacLullich A. M., Brayne C.欧洲流行病学临床病理学研究（EClipSE）合作成员。谵妄与晚年认知能力下降的关系：一项基于3个人群的队列研究的神经病理学研究。JAMA Psychiatry. 2017；74(3): 244 - 251。Hall R. J, Watne L. O, Cunningham E., Zetterberg H., Shenkin S. D., Wyller T. B., MacLullich a . M. J.脑脊液生物标志物在谵妄中的系统评价。国际老年精神病学杂志。2018；33(11): 1479 - 1500。李爱华，穆建良，赵国明，赵春华，赖维奎，金涛，Underwood M.心脏手术后重症监护病房谵妄风险预测模型：系统评价和独立外部验证，中华麻醉学杂志，2017；118(3): 391 - 399。马鲁利奇，沈金，古德克，等。急性内科病人谵妄诊断的4a试验：诊断准确性研究美国国立卫生研究院期刊库；2019年8月（卫生技术评估第23.40期）第五章，4AT的诊断准确性。可从：https://www.ncbi.nlm.nih.gov/books/NBK544921/ Witlox J, Eurelings L. S. M, De Jonghe J. F. M, Kalisvaart K. J, Eikelenboom P.等。老年患者谵妄与出院后死亡率、住院和痴呆的风险：一项荟萃分析《美国医学协会杂志》上。2010年;304:443 - 451。英国国家医疗服务体系批准使用国家早期预警评分（NEWS） 2来提高对急性病人的检测。（2018年2月5日）。2020年10月11日检索自https://www.rcplondon.ac.uk/news/nhs-england-approves-use-national-early-warning-score-news-2-improve-detection-acutely-ill。

Background Delirium is an acute-onset, severe neuropsychiatric syndrome that affects 1 in 8 hospitalised patients. Delirium is associated with higher mortality, new long-term cognitive impairment and worsening of existing neurodegeneration. However, the mechanisms of delirium remains poorly understood. Some studies have suggested a role for inflammation, with raised CSF and inflammatory biomarkers frequently observed. In recent years new clinical tools have been developed to improve the recognition and ascertainment of delirium, such as 4AT and NEWS2. There is also growth in the use of routine data to assess risk and outcomes of delirium, with application of machine learning and AI. These developments allow for new research addressing at unprecedented scale relationships between delirium as coded in routine data and other clinical variables such as markers of inflammation and physiological measurements. What I aim to achieve within the PhD research project: 1) To explore the frequency and representation of reported delirium coding in healthcare discharge summaries via a systematic review 2) Perform research studies examining risks and associated outcomes for delirium using electronic health records that have utilised delirium assessment tools (e.g. NEWS2 and 4AT) o Risk factors including inflammation (via clinical biomarkers), abnormal physiological parameters (such as hypotension and hypoxia) and increased brain atrophy. o Outcomes include 30-day mortality, length of stay, readmission, development of dementia (or new cognitive impairment) and functional decline. References: Davis D. H., Muniz-Terrera G., Keage H. A., Stephan B. C., Fleming J., Ince P. G., Matthews F. E., Cunningham C., Ely E. W., MacLullich A. M., Brayne C. Epidemiological Clinicopathological Studies in Europe (EClipSE) Collaborative Members. Association of Delirium With Cognitive Decline in Late Life: A Neuropathologic Study of 3 Population-Based Cohort Studies. JAMA Psychiatry. 2017; 74(3):244-251.Hall R. J., Watne L. O., Cunningham E., Zetterberg H., Shenkin S. D., Wyller T. B., MacLullich A. M. J. CSF biomarkers in delirium: a systematic review. Int J Geriatr Psychiatry. 2018; 33(11):1479-1500. Lee A., Mu J. L., Joynt G. M., Chiu C. H., W. Lai V. K., Gin T., Underwood M. J. Risk prediction models for delirium in the intensive care unit after cardiac surgery: a systematic review and independent external validation, BJA: British Journal of Anaesthesia. 2017; 118(3):391-399. MacLullich A. M. J., Shenkin SD, Goodacre S., et al. The 4 'A's test for detecting delirium in acute medical patients: a diagnostic accuracy study. NIHR Journals Library; 2019 Aug. (Health Technology Assessment, No. 23.40.) Chapter 5, Diagnostic accuracy of the 4AT. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544921/ Witlox J., Eurelings L. S. M., De Jonghe J. F. M., Kalisvaart K. J., Eikelenboom P., et al. Delirium in elderly patients and the risk of post-discharge mortality, institutionalization, and dementia: A meta-analysis. JAMA. 2010; 304:443-451. NHS England approves use of National Early Warning Score (NEWS) 2 to improve detection of acutely ill patients. (2018, February 05). Retrieved October 11, 2020, from https://www.rcplondon.ac.uk/news/nhs-england-approves-use-national-early-warning-score-news-2-improve-detection-acutely-ill.