Association between components of the delirium syndrome and outcomes in hospitalised adults: a systematic review and meta-analysis.

BACKGROUND: Delirium is a heterogeneous syndrome with inattention as the core feature. There is considerable variation in the presence and degree of other symptom domains such as altered arousal, psychotic features and global cognitive dysfunction. Delirium is independently associated with increased mortality, but it is unclear whether individual symptom domains of delirium have prognostic importance. We conducted a systematic review and meta-analysis of studies in hospitalised adults in general settings to identify the relationship between symptom domains of delirium and outcomes. (PROSPERO: CRD42018093935). METHODS: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, clinicaltrials.gov and the Cochrane Central Register of Controlled Trials from inception to November 2019. We included studies of hospitalised adults that reported associations between symptom domains of delirium and 30-day mortality (primary outcome), and other outcomes including mortality at other time points, length of stay, and dementia. Reviewer pairs independently screened articles, extracted data, and assessed risk of bias (Risk of Bias Assessment tool for Non-randomized Studies) and quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework. We performed random-effects meta-analyses stratified by delirium domain where possible. RESULTS: From 7092 citations we included 6 studies (6002 patients, 1112 with delirium). Higher mortality (ranging from in-hospital to follow-up beyond 12 months) was associated with altered arousal (pooled Odds Ratio (OR) 2.80, 95% Confidence Interval (CI) 2.33-3.37; moderate-quality evidence), inattention (pooled OR 2.57, 95% CI 1.74-3.80; low-quality evidence), and in single studies with disorientation, memory deficits and disorganised thoughts. Risk of bias varied across studies but was moderate-to-high overall, mainly due to selection bias, lack of blinding of assessments and unclear risk of selective outcome reporting. We found no studies on the association between psychotic features, visuospatial deficits or affective disturbances in delirium and outcomes, or studies reporting non-mortality outcomes. CONCLUSIONS: Few studies have related symptom domains of delirium to outcomes, but the available evidence suggests that altered arousal and inattention in delirium are associated with higher mortality than normal arousal and attention in people with or without delirium. Measurable symptom domains of delirium may have value in predicting survival and stratifying patients for treatment. We recommend that future delirium studies report outcomes by symptom domain

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

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis

Abstract Background Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. Methods We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. Results From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). Conclusions Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium

The Diagnosis of Delirium Superimposed on Dementia: An Emerging Challenge

Delirium occurring in patients with dementia is referred to as delirium superimposed on dementia (DSD). People who are older with dementia and who are institutionalized are at increased risk of developing delirium when hospitalized. In addition, their prior cognitive impairment makes detecting their delirium a challenge. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision are considered the standard reference for the diagnosis of delirium and include criteria of impairments in cognitive processes such as attention, additional cognitive disturbances, or altered level of arousal. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision does not provide guidance regarding specific tests for assessment of the cognitive process impaired in delirium. Importantly, the assessment or inclusion of preexisting cognitive impairment is also not addressed by these standards. The challenge of DSD gets more complex as types of dementia, particularly dementia with Lewy bodies, which has features of both delirium and dementia, are considered. The objective of this article is to critically review key elements for the diagnosis of DSD, including the challenge of neuropsychological assessment in patients with dementia and the influence of particular tests used to diagnose DSD. To address the challenges of DSD diagnosis, we present a framework for guiding the focus of future research efforts to develop a reliable reference standard to diagnose DSD. A key feature of a reliable reference standard will improve the ability to clinically diagnose DSD in facility-based patients and research studies

Objective measurement of sedentary behaviour using accelerometers

Background: Sedentary behaviour (SB) is an important risk factor for a number of chronic diseases. Although gaps remain in our knowledge of the elements of SB most associated with reduced health outcomes, measuring SB is important, especially in less active patient populations where treatment-related changes may be seen first in changes in SB.Methods: We review current published work in the measurement of SB to make recommendations for SB measurement in clinical studies.Results: To help move our understanding of the area forward, we propose a set of derived measures of SB that can be easily understood and interpreted.Conclusion: Although there is more work required to determine and validate the most clinically relevant and sensitive measures of SB, there is enough understanding of how to measure SB to enable its inclusion in study protocols

A smartphone-based test for the assessment of attention deficits in delirium: A case-control diagnostic test accuracy study in older hospitalised patients.

BACKGROUND: Delirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients. METHODS: This was a case-control study of hospitalised patients aged ≥65 years with delirium (with or without pre-existing cognitive impairment), who were compared to patients with dementia without delirium, and patients without cognitive impairment. Reference standard delirium assessment, which included a neuropsychological test battery, was based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A separate blinded assessor administered the DelApp arousal assessment (score 0-4) and attention task (0-6) yielding an overall score of 0 to 10 (lower scores indicate poorer performance). Analyses included receiver operating characteristic curves and sensitivity and specificity. Optimal cut-points for delirium detection were determined using Youden's index. RESULTS: A total of 187 patients were recruited, mean age 83.8 (range 67-98) years, 152 (81%) women; n = 61 with delirium; n = 61 with dementia without delirium; and n = 65 without cognitive impairment. Patients with delirium performed poorly on the DelApp (median score = 4/10; inter-quartile range 3.0, 5.5) compared to patients with dementia (9.0; 5.5, 10.0) and those without cognitive impairment (10.0; 10.0, 10.0). Area under the curve for detecting delirium was 0.89 (95% Confidence Interval 0.84, 0.94). At an optimal cut-point of ≤8, sensitivity was 91.7% (84.7%, 98.7%) and specificity 74.2% (66.5%, 81.9%) for discriminating delirium from the other groups. Specificity was 68.3% (56.6%, 80.1%) for discriminating delirium from dementia (cut-point ≤6). CONCLUSION: Patients with delirium (with or without pre-existing cognitive impairment) perform poorly on the DelApp compared to patients with dementia and those without cognitive impairment. A cut-point of ≤8/10 is suggested as having optimal sensitivity and specificity. The DelApp is a promising tool for assessment of attention deficits associated with delirium in older hospitalised adults, many of whom have prior cognitive impairment, and should be further validated in representative patient cohorts

Validation of the 4AT tool for delirium assessment in specialist palliative care settings: protocol of a prospective diagnostic test accuracy study [version 1; peer review: 2 approved]

BACKGROUND: Delirium is a serious and distressing neuropsychiatric condition, which is prevalent across all palliative care settings. Hypoactive delirium is particularly common, but difficult to recognize, partly due to overlapping symptoms with depression and dementia. Delirium screening tools can lead to earlier identification and hence better management of patients. The 4AT (4 ‘A’s Test) is a brief tool for delirium detection, designed for use in clinical practice. It has been validated in 17 studies in over 3,700 patients. The test is currently used in specialist palliative care units, but has not been validated in this setting. The aim of the study is to determine the diagnostic accuracy of the 4AT for delirium detection against a reference standard, in hospice inpatients. METHODS: 240 participants will be recruited from the inpatient units of two hospices in Scotland. If a patient lacks capacity to consent, agreement will be sought from a legal proxy. Each participant will complete the 4AT and a reference standard assessment based on the diagnostic delirium criteria in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). This will be supplemented by tests of cognition and attention, including reverse days of the week, counting down from 20 to 1, Vigilance 'A', the Observational Scale for Level of Arousal, the modified Richmond Agitation Sedation Scale and the Delirium Rating Scale-Revised-98. The assessments will be conducted in a randomized order by two independent clinicians, who will be blinded to the results until both are complete. Primary outcomes will be the sensitivity and specificity of the 4AT in detecting delirium. DISCUSSION: The findings will inform clinical practice regarding delirium assessment in palliative care settings. TRIAL REGISTRATION: ISRCTN ISRCTN97417474 (21/02/2020)

Diagnostic test accuracy of a novel smartphone application for the assessment of attention deficits in delirium in older hospitalised patients: a prospective cohort study protocol.

BACKGROUND: Delirium is a common and serious clinical syndrome which is often missed in routine clinical care. The core cognitive feature is inattention. We developed a novel bedside neuropsychological test for assessing inattention in delirium implemented on a smartphone platform (DelApp). We aim to evaluate the diagnostic performance of the DelApp in a representative cohort of older hospitalised patients. METHODS: This is a prospective study of older non-scheduled hospitalised patients (target n = 500, age ≥ 65), recruited from elderly care and acute orthopaedic wards. Exclusion criteria are: non-English speakers; severe vision or hearing impairment; photosensitive epilepsy. A structured reference standard delirium assessment based on DSM-5 criteria will be used, which includes a cognitive test battery administered by a trained assessor (Orientation-Memory-Concentration Test, Abbreviated Mental Test-10, Delirium Rating Severity Scale-Revised-98, digit span, months and days backwards, Vigilance A' test) and assessment of arousal (Observational Scale of Level of Arousal, Richmond Agitation Sedation Scale). Prior change in cognition will be documented using the Informant Questionnaire on Cognitive Decline in the Elderly. Patients will be categorized as delirium (with/without dementia), possible delirium, dementia, no cognitive impairment, or undetermined. A separate assessor (blinded to diagnosis and assessments) will administer the DelApp index test within 3 h of the reference standard assessment. The DelApp comprises assessment of arousal (score 0-4) and sustained attention (score 0-6), yielding a total score between 0 and 10 (higher score = better performance). Outcomes (length of stay, mortality and discharge location) will be collected at 12 weeks. We will evaluate a priori cutpoints derived from a previous case-control study. Measures of the accuracy of DelApp will include sensitivity, specificity, positive and negative predictive values, and area under the ROC curve. We plan repeat assessments on up to 4 occasions in a purposive subsample of 30 patients (15 delirium, 15 no delirium) to examine changes over time. DISCUSSION: This study evaluates the diagnostic test accuracy of a novel smartphone test for delirium in a representative cohort of older hospitalised patients, including those with dementia. DelApp has the potential to be a convenient, objective method of improving delirium assessment for older people in acute care. TRIAL REGISTRATION: Clinical trials.gov, NCT02590796 . Registered on 29 Oct 2015. Protocol version 5, dated 25 July 2016

Effects of caffeine on reaction time are mediated by attentional rather than motor processes

Background Caffeine has a well-established effect on reaction times (RTs) but the neurocognitive mechanisms underlying this are unclear. Methods In the present study, 15 female participants performed an oddball task after ingesting caffeine or a placebo, and electroencephalographic data were obtained. Single-trial P3b latencies locked to the stimulus and to the response were extracted and mediation models were fitted to the data to test whether caffeine’s effect on RTs was mediated by its effect on either type of P3b latencies. Results Stimulus-locked latencies showed clear evidence of mediation, with approximately a third of the effect of caffeine on RTs running through the processes measured by stimulus-locked latencies. Caffeine did not affect response-locked latencies, so could not mediate the effect. Discussion These findings are consistent with caffeine’s effect on RTs being a result of its effect on perceptual-attentional processes, rather than motor processes. The study is the first to apply mediation analysis to single-trial P3b data and this technique holds promise for mental chronometric studies into the effects of psychopharmacological agents. The R code for performing the single trial analysis and mediation analysis are included as supplementary materials