Delirium in nursing home residents: is there a role of antidepressants? A cross sectional study.

BACKGROUND: Delirium is strongly associated with poor health outcomes, yet it is frequently underdiagnosed. Limited research on delirium has been conducted in Nursing Homes (NHs). Our aim is to assess delirium prevalence and its associated factors, in particular pharmacological prescription, in this care setting. METHODS: Data from the Italian "Delirium Day" 2016 Edition, a national multicenter point-prevalence study on patients aged 65 and older were analyzed to examine the associations between the prevalence of delirium and its subtypes with demographics and information about medical history and pharmacological treatment. Delirium was assessed using the Assessment test for delirium and cognitive impairment (4AT). Motor subtype was evaluated using the Delirium Motor Subtype Scale (DMSS). RESULTS: 955 residents, from 32 Italian NHs with a mean age of 84.72 ± 7.78 years were included. According to the 4AT, delirium was present in 260 (27.2%) NHs residents, mainly hyperactive (35.4%) or mixed subtypes (20.7%). Antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs) was associated with lower delirium prevalence in univariate and multivariate analyses. CONCLUSIONS: The high prevalence of delirium in NHs highlights the need to systematically assess its occurrence in this care settings. The inverse association between SSRIs and delirium might imply a possible preventive role of this class of therapeutic agents against delirium in NHs, yet further studies are warranted to ascertain any causal relationship between SSRIs intake and reduced delirium incidence.

Diagnostic Accuracy of the Recognizing Acute Delirium as Part of Your Routine (RADAR) Scale for Delirium Assessment in Hospitalized Older Adults: A Cross-Sectional Study.

Delirium is highly prevalent among hospitalized older adults and is associated with unfavorable outcomes. However, delirium often remains undiagnosed in the hospital context. Having a valid, simple, and fast screening tool could help in limiting the additional workload for healthcare professionals, without leaving delirium undetected. The aim of this study was to estimate the sensitivity and specificity of the Recognizing Acute Delirium As part of your Routine (RADAR) scale in an Italian hospital. An observational cross-sectional study was conducted. A total of 150 patients aged ≥70 years were enrolled. Receiver operating characteristic (ROC) curves using the Confusion Assessment Method (CAM) criterion-defined delirium as the gold standard were plotted to evaluate the performance of the RADAR scale. The cut-off suggested by previous research was used to estimate the sensitivity, specificity, and positive and negative predictive values of the RADAR scale. The involved patients were mostly females (60%; n = 90), with a median age of 84 years (I-III quartiles: 80-88). According to the CAM and the RADAR scale, 37 (25%) and 58 (39%) patients were classified as experiencing delirium, respectively. The area under the ROC curve of the RADAR scale was 0.916. Furthermore, the RADAR scale showed robust sensitivity (95%), specificity (80%), and positive (60%) and negative predictive values (98%). The RADAR scale is thus suggested to be a valid tool for screening assessment of delirium in hospitalized older adults.

The 4AT, a rapid delirium detection tool for use in hospice inpatient units: Findings from a validation study.

BACKGROUND: Delirium is a serious neuropsychiatric syndrome with adverse outcomes, which is common but often undiagnosed in terminally ill people. The 4 'A's test or 4AT (www.the4AT.com), a brief delirium detection tool, is widely used in general settings, but validation studies in terminally ill people are lacking. AIM: To determine the diagnostic accuracy of the 4AT in detecting delirium in terminally ill people, who are hospice inpatients. DESIGN: A diagnostic test accuracy study in which participants underwent the 4AT and a reference standard based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. The reference standard was informed by Delirium Rating Scale Revised-98 and tests assessing arousal and attention. Assessments were conducted in random order by pairs of independent raters, blinded to the results of the other assessment. SETTING/PARTICIPANTS: Two hospice inpatient units in Scotland, UK. Participants were 148 hospice inpatients aged ⩾18 years. RESULTS: A total of 137 participants completed both assessments. Three participants had an indeterminate reference standard diagnosis and were excluded, yielding a final sample of 134. Mean age was 70.3 (SD = 10.6) years. About 33% (44/134) had reference standard delirium. The 4AT had a sensitivity of 89% (95% CI 79%-98%) and a specificity of 94% (95% CI 90%-99%). The area under the receiver operating characteristic curve was 0.97 (95% CI 0.94-1). CONCLUSION: The results of this validation study support use of the 4AT as a delirium detection tool in hospice inpatients, and add to the literature evaluating methods of delirium detection in palliative care settings. TRIAL REGISTRY: ISCRTN 97417474.

Detection of delirium in older patients-A point prevalence study in surgical and non-surgical hospital wards.

AIMS AND OBJECTIVES: To (i) determine the prevalence of delirium and identify delirium subtypes in surgical and non-surgical patients aged ≥65 years, (ii) determine whether certain precipitating factors affect the prevalence of delirium and (iii) review patients' medical records for description of delirium symptoms and the presence of International Classification of Diseases (ICD-10) coding for delirium in discharge summaries. METHODOLOGICAL DESIGN AND JUSTIFICATIONS: Despite being a robust predictor of morbidity and mortality in older adults, delirium might be inadequately recognised and under-reported in patients' medical records and discharge summaries. A point prevalence study (24-h) of patients ≥65 years from surgical and non-surgical wards was therefore conducted in a tertiary university hospital. ETHICAL ISSUES AND APPROVAL: The study was approved by the Data Protection Officer at the university hospital (2018/3454). RESEARCH METHODS, INSTRUMENTS AND/OR INTERVENTIONS: Patients were assessed for delirium with 4AT and delirium subtypes with the Delirium Motor Subtype Scale. Information about room transfers, need and use of sensory aids and medical equipment was collected onsite. Patients' medical records were reviewed for description of delirium symptoms and of ICD-10 codes. RESULTS: Overall, 123 patients were screened (52% female). Delirium was identified in 27% of them. Prevalence was associated with advanced age (≥85 years). The uncharacterised delirium subtype was most common (36%), followed by hypoactive (30%), hyperactive (24%) and mixed (9%). There were significant associations between positive screening tests and the need and use of sensory aids. Delirium symptoms were described in 58% of the patients who tested positive for delirium and the ICD-10 code for delirium was registered in 12% of these patients' discharge summaries. CONCLUSIONS: The high prevalence of delirium and limited use of discharge codes highlight the need to improve the identification of delirium in hospital settings and at discharge. Increased awareness and detection of delirium in hospital settings are vital to improve patient care.

A survey of non-consultant hospital doctors' perspectives, knowledge, and practices toward delirium in a large Irish hospital.

BACKGROUND: Delirium is a common condition in hospitals, particularly among older people. This refers to a dramatic decline in mental capabilities, which is marked by diminished concentration and consciousness. AIM: The purpose of this study was to assess the views, knowledge, and behavior of non-consultant hospital doctors in managing delirium in a large Irish hospital. METHODS: Questionnaires were administered to 28 healthcare professionals from various departments according to Davis and MacLullich (Age Ageing 38(5):559-563, 2009). It was conducted between July and September 2023, with an emphasis on determining the prevalence rate, diagnostic criteria, and management strategies for delirium. RESULTS: The study established that the majority of respondents recognized the importance of delirium, but there appears to be a gap in the practical management of this clinical syndrome. Although many doctors agreed that delirium was significant, most lacked confidence in its diagnosis and management. The use of standardized assessment tools, such as the 4AT, was limited. CONCLUSIONS: This study highlights the disparity between what is known and practiced by hospital doctors regarding delirium care. This implies increased training for delirium management with frequent use of assessment tools and ongoing education aimed at enhancing patient outcomes in cases of delirium.

Validation of a viable delirium detection test performed by nurses and physicians during routine patient care.

BACKGROUND: Delirium is a frequent mental impairment in geriatric patients hospitalized in acute care facilities. It carries a high risk of complications and is often the first symptom of acute illness. It is clearly important to identify the development of delirium at an early stage, and several short and effective diagnostic tests have been developed and validated for this purpose. Despite this, patients on hospital wards are seldom monitored for signs of emergent delirium, suggesting that compliance with guidelines would be improved by introducing a simpler and more user-friendly test. METHODS: We recently implemented a simple delirium assessment tool, called RMA that can be introduced into the daily routine of ward staff without significantly adding to their workload. The nurses noted their impression of the patient's cognitive state in the electronic medical record, and during the morning round the ward physician administered a short attention test to any patients suspected of new cognitive impairment. In this study, we compared RMA test against the widely used and well validated 4AT. RESULTS: RMA performed daily by the ward staff was found to be non-inferior to 4AT performed by an experienced rater. Compared to 4AT, R&M had a sensitivity of 93.9% and a specificity of 98.3%. An Altman-Bland plot indicated that both tests can be used interchangeably. CONCLUSIONS: The RMA test is reliable, easy to administer, likely to boost compliance with guidelines, and is expected to raise awareness of delirium among the nurses and physicians directly involved in the diagnostic process.

Spanish transcultural adaptation of the 4AT score for the evaluation of delirium in the emergency department: a prospective diagnostic test accuracy study.

BACKGROUND: Delirium is one of the most common adverse events in older people during hospitalization, especially in the emergency department. Reliable, easy-to-use instruments are necessary to properly manage delirium in this setting. This study aims to evaluate the diagnostic validity of the Spanish version of the 4 'A's Test (4AT) in the ED. METHODS: A diagnostic accuracy study was conducted in patients over 65 years old admitted to the Emergency Department who did not have a formal diagnosis of dementia or a severe mental health disorder. Face and content validity were evaluated by an expert panel. Emergency nurses performed the evaluation with 4AT, whilst blinded and trained researchers assessed patients with the Revised Delirium Rating Scale as the gold standard. The content validity index, sensitivity, specificity, positive and negative predictive values, likelihood ratios, Youden's Index and ROC curves were calculated to evaluate the diagnostic accuracy of the instrument. RESULTS: Of 393 eligible patients, 380 were finally analyzed. Content validity yielded a median content validity index of 4 (interquartile range: 0). The Spanish 4AT sensitivity (95.83%; 95% ECI: 78.9-99.9%), specificity (92.98%; 95% CI: 89.8-95.4%), positive predictive value (47.92%) and negative predictive value (99.7%) were satisfactory. Youden's index was 0.89. Positive likelihood ratio was 13.65, and negative likelihood ratio 0.045. The area under the curve was 0.97. CONCLUSIONS: The Spanish version of the 4AT for use in the Emergency Departments is easy-to-use and applicable. The validation results indicate that it is a valid instrument with sufficient predictive validity to identify patients at risk of delirium in the Emergency Departments. Moreover, it is a tool that facilitates the management of an adverse event that is associated with increased mortality and morbidity.

Clinical assessment and short-term mortality prediction of older adults with altered mental status using RASS and 4AT tools.

BACKGROUND: Altered mental status (AMS) in older adults is a common reason for admission to emergency departments (EDs) and usually results from delirium, stupor, or coma. It is important to proficiently identify underlying factors and anticipate clinical outcomes for those patients. AIM: The primary objective of this study was to reveal and compare the clinical outcomes and etiologic factors of older patients with delirium, stupor, and coma. The secondary objective was to identify the 30-day mortality risk for those patients. METHOD: The study was conducted as prospective and observational research. We included patients aged 65 years and older who presented with new-onset neurological and cognitive symptoms or worsening in baseline mental status. Patients who presented no change in their baseline mental status within 48 h and those who needed urgent interventions were excluded. Selected patients were assessed using RASS and 4AT tools and classified into three groups: stupor/coma, delirium, and no stupor/coma or delirium (no-SCD). Appropriate statistical tests were applied to compare these 3 groups. The 30-day mortality risks were identified by Cox survival analysis and Kaplan-Meier curve. RESULTS: A total of 236 patients were eligible for the study. Based on their RASS and 4AT test scores: 56 (23.7%), 94 (40.6%), and 86 (36.4%) patients formed the stupor/coma, delirium and no-SCD groups, respectively. There was no statistical difference in the three groups for gender, mean age, and medical comorbidities. Neurological (34.7%), infectious (19.4%), and respiratory (19.0%) diseases were the leading factors for AMS. Post-hoc tests showed that CCI scores of the delirium (6, IQR = 3) and stupor/coma (7, IQR = 3) groups were not significantly different. The 30-day mortality rates of stupor/coma, delirium, and no-SCD groups were 42.%, 15.9%, and 12.8%, respectively (p < 0.005). The hazard ratio of the stupor/coma group was 2.79 (CI: 95%, 1.36-5.47, p = 0.005). CONCLUSION: AMS remains a significant clinical challenge in EDs. Using the RASS and 4AT tests provides benefits and advantages for emergency medicine physicians. Neurological, infectious, and respiratory diseases can lead to life-threatening mental deterioration. Our study revealed that long-term mortality predictor CCI scores were quite similar among patients with delirium, stupor, or coma. However, the short-term mortality was significantly increased in the stupor/coma patients and they had 2.8 times higher 30-day mortality risk than others.

Diagnostic accuracy of the Dutch version of the 4AT for delirium detection in a mixed patient population and setting.

BACKGROUND: Delirium is an acute disturbance in attention, awareness and cognition. Immediate detection in older adults is recommended because delirium is associated with adverse outcomes. The 4 'A's Test (4AT) is a short screening instrument for delirium. The aim of this study is to evaluate diagnostic accuracy of the Dutch version of the screening tool 4AT for delirium detection in different settings. METHODS: Prospective observational study conducted in two hospitals in patients aged ≥ 65 years in geriatric wards and the Emergency Department (ED). Each participant underwent two assessments; the index test 4AT, followed by the reference standard for delirium performed by a geriatric care specialist. The reference standard delirium is according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria. RESULTS: A total of 71 geriatric inpatients and 49 older ED patients were included. The prevalence of delirium was 11.6% in the acute geriatric ward and 6.1% in the ED. The sensitivity and specificity of the 4AT in the acute geriatric ward were 0.88 and 0.69, respectively. In the ED, the sensitivity and specificity were 0.67 and 0.83, respectively. The area under the receiver operating characteristic curve was 0.80 for the acute geriatric ward setting and 0.74 for the ED setting. CONCLUSION: The Dutch version of the 4AT is a reliable screening tool for delirium detection in both acute geriatric wards and ED. Due to its brevity and practicality (i.e., no special training is required to administer the tool), it is useful in clinical practice.

A systematic review of studies reporting on neuropsychological and functional domains used for assessment of recovery from delirium in acute hospital patients.

OBJECTIVES: Assessing for recovery in delirium is essential in guiding ongoing investigation and treatment. Yet, there is little scrutiny and no research or clinical consensus on how recovery should be measured. We reviewed studies which used tests of neuropsychological domains and functional ability to track recovery of delirium longitudinally in acute hospital settings. METHODS/DESIGN: We systematically searched databases (MEDLINE, PsycInfo, CINAHL, Embase, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials), from inception to October 14th , 2022. Inclusion criteria were: adult acute hospital patients (≥18 years) diagnosed with delirium by a validated tool; 1+ repeat assessment using an assessment tool measuring domains of delirium/functional recovery ≤7 days from baseline. Two reviewers independently screened articles, performed data extraction, and assessed risk of bias. A narrative data synthesis was completed. RESULTS: From 6533 screened citations, we included 39 papers (reporting 32 studies), with 2370 participants with delirium. Studies reported 21 tools with an average of four repeat assessments including baseline (range 2-10 assessments within ≤7 days), measuring 15 specific domains. General cognition, functional ability, arousal, attention and psychotic features were most commonly assessed for longitudinal change. Risk of bias was moderate to high for most studies. CONCLUSIONS: There was no standard approach for tracking change in specific domains of delirium. The methodological heterogeneity of studies was too high to draw firm conclusions on the effectiveness of assessment tools to measure delirium recovery. This highlights the need for standardised methods for assessing recovery from delirium.

Delirium screening in a stroke unit by nurses using 4AT: Results from a quality improvement project.

AIM: To assess the feasibility of delirium screening with the screening tool 4AT conducted by stroke unit nurses. DESIGN: Observational. METHODS: Patients with confirmed acute stroke admitted to the stroke unit at Baerum Hospital, Norway, from March to October 2020, were consecutively recruited. Nurses performed delirium screening using the rapid screening tool 4AT within 24 h of admission, at discharge and when delirium was suspected, and filled out a questionnaire assessing their experiences with the delirium screening. A geriatrician validated the delirium diagnosis. RESULTS: In all, 62 patients were included, mean age 73.3 years. 4AT was performed according to protocol in 49 (79.0%) and 39 (62.9%) patients at admission and discharge respectively. Lack of time (40%) was reported as the most common reason for not performing delirium screening. The nurses reported that the felt competent to carry out the 4AT screening, and did not experience it as significant extra workload. Five patients (8%) were diagnosed with delirium. Delirium screening performed by stroke unit nurses seemed feasible and the nurses experienced that 4AT was a useful tool for this purpose.

Risk Factors and 120-Day Functional Outcomes of Delirium After Hip Fracture Surgery: A Prospective Cohort Study Using the UK National Hip Fracture Database (NHFD).

OBJECTIVES: To identify risk factors of postoperative delirium among hip fracture patients with normal preoperative cognition, and examine associations with returning home or recovery of mobility. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: We used the National Hip Fracture Database (NHFD) to identify patients presenting with hip fracture in England (2018-2019), but excluded those with abnormal cognition [abbreviated mental test score (AMTS) < 8] on presentation. METHODS: We examined the results of routine delirium screening performed using the 4 A's Test (4AT), to assess alertness, attention, acute change, and orientation in a 4-item mental test. Associations between 4AT score and return home or to outdoor mobility at 120 days were estimated, and risk factors identified for abnormal 4AT scores: (1) 4AT ≥4 suggesting delirium and (2) 4AT = 1-3 being an intermediate score not excluding delirium. RESULTS: Overall, 63,502 patients (63%) had a preoperative AMTS ≥8, in whom a postoperative 4AT score ≥4 suggestive of delirium was seen in 4454 (7%). These patients were less likely to return home [odds ratio (OR), 0.46; 95% CI, 0.38-0.55] or regain outdoor mobility (OR, 0.63; 95% CI, 0.53-0.75) by 120 days. Multiple factors including any deficit in preoperative AMTS and malnutrition were associated with higher risk of 4AT ≥4, while use of preoperative nerve blocks was associated with lower risk (OR, 0.88; 95% CI, 0.81-0.95). Poorer outcomes were also seen in 12,042 (19%) patients with 4AT = 1-3; additional risk factors associated with this score included socioeconomic deprivation and surgical procedure types that were not compliant with National Institute of Health and Care Excellence guidance. CONCLUSION AND IMPLICATIONS: Delirium after hip fracture surgery significantly reduces the likelihood of returning home or to outdoor mobility. Our findings underline the importance of measures to prevent postoperative delirium, and aid the identification of high-risk patients for whom delirium prevention might potentially improve outcomes.

Diagnostic accuracy of the "4 A's Test" delirium screening tool for the postoperative cardiac surgery ward.

BACKGROUND: Delirium is prevalent and underdetected among cardiac surgery patients on the postoperative ward. This study aimed to validate the 4 A's Test delirium screening tool and evaluate its accuracy both when used by research assistants and when subsequently implemented by nursing staff on the ward. METHODS: This single-center, prospective observational study evaluated the performance of the 4 A's Test administered by research assistants (phase 1) and nursing staff (phase 2). Assessments were undertaken during the patients' first 3 postoperative days on the postcardiac surgery ward along with previous routine nurse-led Confusion Assessment Method assessments. These index tests were compared with a reference standard diagnosis of delirium based on Diagnostic and Statistical Manual of Mental Disorders 5th Edition criteria. Surveys regarding delirium screening were administered to nurses pre- and postimplementation of the 4 A's Test in phase 2 of the study. RESULTS: In phase 1, a total of 137 patients were enrolled, of whom 24.8% experienced delirium on the postoperative cardiac ward. The 4 A's Test had a sensitivity of 85% (95% confidence interval, 73-93) and a specificity of 90% (95% confidence interval, 85-93) compared with the reference standard. The nurse-assessed Confusion Assessment Method had a sensitivity of 23% (95% confidence interval, 13-37) and specificity of 100% (95% confidence interval, 99-100). In phase 2, nurses (n = 51) screened 179 patients for delirium using the 4 A's Test. Compared with the reference rater, the 4 A's Test had a sensitivity of 58% (95% confidence interval, 28-85) and specificity of 94% (95% confidence interval, 85-98). Postimplementation, 64% of nurses thought that the 4 A's Test improved their confidence in delirium detection, and 76% of nurses would consider routine 4 A's Test use. CONCLUSIONS: The 4 A's Test demonstrated moderate sensitivity and high specificity to detect delirium in a real-world setting after cardiac surgery on the postoperative ward. A modified model of use with less frequent administration, along with increased engagement of the postoperative team, is recommended to improve early delirium detection on the cardiac surgery postoperative ward.

Diagnostic accuracy of the 4AT for delirium: A systematic review and meta-analysis.

INTRODUCTION: Despite common, serious, costly, and often fatal conditions affecting up to 50 % of older patients, delirium is often unrecognized and overlooked. We examine the accuracy of the 4AT for detecting older patients with delirium. METHODS: We performed a systematic search of PubMed, Web of Science, PsycINFO, and EMBASE databases from inception to April 2020 and updated to January 2022. Four independently reviewers extracted study data and assessed the methodological quality using the revised quality assessment of diagnostic accuracy studies tool (QUADAS-2). Pooled estimates of sensitivity and specificity were generated using a bivariate random effects model. All statistical analyses were performed with STATA version 15.1 and Meta-DiSc version 1.4 software. RESULTS: Eleven studies with 2789 participants were included. The pooled sensitivity and specificity were 0.87 (95 % CI: 0.81-0.91) and 0.87 (95 % CI: 0.79-0.92), respectively, and the positive and negative likelihood ratios were 6.66 (95 % CI: 4.12-10.74) and 0.15 (95 % CI: 0.10-0.23), respectively. Deeks' test indicated no significant publication bias (t = 0.83, P = 0.43). Univariable meta-regression showed that patient selection and flow and timing significantly influenced the pooled sensitivity (P < 0.05), settings significantly influenced the pooled specificity (P < 0.05). CONCLUSION: Our meta-analysis demonstrates that 4AT is a sensitive and specific screening tool for delirium in older patients. Its brevity and simplicity support its use in routine clinical practice, particularly in time-poor settings. Clinicians should come to a conclusion based largely on the 4AT findings in conjunction with clinical judgment.

Exploration of delirium assessment and management in a hospice inpatient unit.

Background: Delirium is common across all palliative care settings. Guidelines exist to support the care of terminally ill people who develop delirium; yet the evidence base is limited. Recent surveys of palliative care specialists have suggested clinical practice is variable. Aim: To explore delirium assessment and management in a hospice inpatient setting. Methods: A mixed-methods study comprising a retrospective case note review of 21 patients admitted to a hospice inpatient unit and semi-structured interviews with seven hospice inpatient doctors and nurses. Results: A total of 62% of patients were screened for delirium on admission using the 4 As tool (4AT). The period prevalence of delirium was 76% during the 2-week study period. The term 'delirium' was documented infrequently in case notes, compared to other more ambiguous terms. Interview data suggested that nurses were unfamiliar with delirium screening tools. Conclusion: Lack of awareness about delirium screening tools and the infrequent use of the term 'delirium' may suggest that delirium goes under-recognised and under-treated. Further education and research are required to support the care of terminally ill people with delirium.

NEWS2 shows low sensitivity and high specificity for delirium detection: a single site observational study of 13,908 patients.

Delirium affects 25% of hospital admissions of older people and is a serious medical condition with poor outcomes. 'New confusion' as a delirium indicator was incorporated into the 'alert, verbal, pain and unresponsive' (AVPU) level of consciousness scale in the National Early Warning Score 2 (NEWS2) in 2017. We measured sensitivity of non-alert NEWS2 (new confusion and/or V, P or U ratings) for delirium through comparison with the four 'A's test (4AT) delirium tool in 13,908 consecutive non-elective hospital admissions. We included NEWS2 scores 4 hours before or after 4AT. There were 2,802 (20%) admissions with positive 4AT and 594 (4.3%) with non-alert NEWS2 status. Sensitivity of NEWS2 for 4AT ≥4 was 17.8% (95% confidence interval (CI) 16.4-19.2), and specificity was 99.1% (95% CI 98.9-99.3). These findings suggest that NEWS2 in current practice has low sensitivity but high specificity for delirium. Further research is needed to improve routine inpatient monitoring for delirium.

A prospective study of remote delirium screening using the modified K-4AT for COVID-19 inpatients.

Background: Delirium is a neuropsychiatric condition strongly associated with poor clinical outcomes such as high mortality and long hospitalization. In the patients with Coronavirus disease 2019 (COVID-19), delirium is common and it is considered as one of the risk factors for mortality. For those admitted to negative-pressure isolation units, a reliable, validated and contact-free delirium screening tool is required. Materials and methods: We prospectively recruited eligible patients from multiple medical centers in South Korea. Delirium was evaluated using the Confusion Assessment Method (CAM) and 4'A's Test (4AT). The attentional component of the 4AT was modified such that respondents are required to count days, rather than months, backward in Korean. Blinded medical staff evaluated all patients and determined whether their symptoms met the delirium criteria of the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5). An independent population of COVID-19 patients was used to validate the 4AT as a remote delirium screening tool. We calculated the area under the receiver operating characteristic curve (AUC). Results: Out of 286 general inpatients, 28 (9.8%) inpatients had delirium. In this population, the patients with delirium were significantly older (p = 0.018) than the patients without delirium, and higher proportion of males were included in the delirium group (p < 0.001). The AUC of the 4AT was 0.992 [95% confidence interval (CI) 0.983-1.000] and the optimal cutoff was at 3. Of the independent COVID-19 patients, 13 of 108 (12.0%) had delirium. Demographically, the COVID-19 patients who had delirium only differed in employment status (p = 0.047) from the COVID-19 patients who did not have delirium. The AUC for remote screening using the 4AT was 0.996 (0.989-1.000). The optimal cutoff of this population was also at 3. Conclusion: The modified K-4AT had acceptable reliability and validity when used to screen inpatients for delirium. More importantly, the 4AT efficiently screened for delirium during remote evaluations of COVID-19 patients, and the optimal cutoff was 3. The protocol presented herein can be used for remote screening of delirium using the 4AT.

Role of interferons (IFNs) in the differentiation of T peripheral helper (Tph) cells.

Interleukin (IL)-21-producing T peripheral helper (Tph) cells are thought to contribute to extra-follicular B cell activation and play a pathogenic role in autoimmune diseases. In this study, we investigated the relationship between Tph cells and interferons (IFNs) in several autoimmune diseases because our previous study demonstrated that type I IFNs promote the differentiation of IL-21-producing Tph-like cells. The frequency of Tph cells in the blood as well as serum IFN-α2a and IFN-λ1 were markedly elevated in patients with active systemic lupus erythematosus (SLE) compared to other autoimmune diseases or healthy controls. Notably, the frequency of Tph cells was positively correlated with the SLE disease activity index, serum IFN-α and serum IFN-λ1 in SLE patients. Additionally, we found that type III IFNs (IFN-λ1, IFN-λ2 and IFN-λ3) promote the differentiation of programmed cell death-1 (PD-1)+ CXCR5 -CD4+ T cells and enhance the secretion of IL-21, IFN-γ and CXCL13. IFN-λ1, like IFN-α, up-regulated the mRNA expression of IL21, IFNG, CXCL13, CD244, SLAMF7, GZMB, PRF1, CCR5 and PRDM1, whereas it down-regulated that of CXCR5 and BCL6, reflecting a Tph-related gene expression pattern. IFN-α in combination with IFN-λ1, IFN-λ2 or IFN-λ3 significantly increased the differentiation of PD-1+CXCR5- Tph-like cells and the secretion of Tph-related cytokines as compared with each IFN alone, suggesting a cooperative interaction. From these findings, it is highly probable that type III IFNs in addition to type I IFNs play a key role in the differentiation of Tph cells and that high levels of IFN-α and IFN-λ1 trigger the differentiation and expansion of Tph cells in SLE.

A variety of 'exhausted' T cells in the tumor microenvironment.

In T-cell biology, 'exhaustion' was initially described as a hyporesponsive state in CD8+ T cells during chronic infections. Recently, exhaustion has been recognized as a T-cell dysfunctional state in the tumor microenvironment (TME). The term 'exhaustion' is used mainly to refer to effector T cells with a reduced capacity to secrete cytokines and an increased expression of inhibitory receptors. The up-regulation of exhaustion-related inhibitory receptors, including programmed cell death protein 1 (PD-1), in such T cells has been associated with the development of tumors, prompting the development of immune checkpoint inhibitors. In addition to CD8+ T cells, CD4+ T cells, including the regulatory T (Treg) cell subset, perform a wide variety of functions within the adaptive immune system. Up-regulation of the same inhibitory receptors that are associated with CD8+ T-cell exhaustion has also been identified in CD4+ T cells in chronic infections and cancers, suggesting a similar CD4+ T-cell exhaustion phenotype. For instance, high expression of PD-1 has been observed in Treg cells in the TME, and such Treg cells can play an important role in the resistance to PD-1 blockade therapies. Furthermore, recent progress in single-cell RNA sequencing has shown that CD4+ T cells with cytotoxic activity are also vulnerable to exhaustion. In this review, we will discuss novel insights into various exhausted T-cell subsets, which could reveal novel therapeutic targets and strategies to induce a robust anti-tumor immune response.

Positive scores on the 4AT delirium assessment tool at hospital admission are linked to mortality, length of stay and home time: two-centre study of 82,770 emergency admissions.

BACKGROUND: Studies investigating outcomes of delirium using large-scale routine data are rare. We performed a two-centre study using the 4 'A's Test (4AT) delirium detection tool to analyse relationships between delirium and 30-day mortality, length of stay and home time (days at home in the year following admission). METHODS: The 4AT was performed as part of usual care. Data from emergency admissions in patients ≥65 years in Lothian, UK (n = 43,946) and Salford, UK (n = 38,824) over a period of $\sim$3 years were analysed using logistic regression models adjusted for age and sex. RESULTS: 4AT completion rates were 77% in Lothian and 49% in Salford. 4AT scores indicating delirium (≥4/12) were present in 18% of patients in Lothian, and 25% of patients in Salford. Thirty-day mortality with 4AT ≥4 was 5.5-fold greater than the 4AT 0/12 group in Lothian (adjusted odds ratio (aOR) 5.53, 95% confidence interval [CI] 4.99-6.13) and 3.4-fold greater in Salford (aOR 3.39, 95% CI 2.98-3.87). Length of stay was more than double in patients with 4AT scores of 1-3/12 (indicating cognitive impairment) or ≥ 4/12 compared with 4AT 0/12. Median home time at 1 year was reduced by 112 days (Lothian) and 61 days (Salford) in the 4AT ≥4 group (P < 0.001). CONCLUSIONS: Scores on the 4AT used at scale in practice are strongly linked with 30-day mortality, length of hospital stay and home time. The findings highlight the need for better understanding of why delirium is linked with poor outcomes and also the need to improve delirium detection and treatment.