MICA: Development of a software application for detection and monitoring of attentional deficits in delirium

Lead Research Organisation: University of Edinburgh
Department Name: School of Clinical Sciences

Abstract

Delirium is an acute, severe deterioration in mental functioning affecting at least 1 in 8 general acute hospital inpatients, and at least 1 in 3 intensive care unit inpatients. It is associated with considerable patient and carer distress and other poor outcomes such as longer stay in hospital. Despite its importance, delirium is grossly under-detected in acute hospitals, with less than 1 in 3 detected.

Several validated tools for the assessment of delirium are available. However, there is a lack of detailed research on means of objectively measuring inattention, the key cognitive deficit in delirium. Some commonly-used cognitive tests can reliably detect inattention, but mostly they do not clearly discriminate delirium from dementia. Also, there is a lack of knowledge on grading the severity of inattention, and monitoring attentional function over time in order to assess change in the patient. These important gaps contribute to the under-detection of delirium in clinical practice.

To address these gaps, we developed a new test for the measurement of inattention in delirium, implemented on a purpose-built computerised device called the Delbox. The test involves counting sequences of slowly-presented lights. We found that the Delbox detects delirium successfully, and also discriminates delirium from dementia. Our studies found that patients with dementia perform similarly on this test to cognitively healthy volunteers.

Although the Delbox is effective, tests on devices that are universally available have potential for far greater impact. Therefore, we have now developed a prototype software application (DelApp) for smartphones based on the same tests.

A feasibility study in 20 hospital patients showed highly comparable performance between the Delbox and the DelApp. Further studies of the DelApp in 156 general ward patients showed that patients with delirium had statistically significantly lower scores compared to patients with dementia or cognitively normal volunteers. A statistic called the Area Under the Receiver Operating Characteristic Curve (AUC) used to assess performance of diagnostic tests had a value of 0.99, which indicates excellent performance. We have also recently completed a feasibility study of the DelApp in 47 patients in the intensive care unit (20 with delirium). Delirium was associated with statistically significantly lower DelApp scores, and an AUC figure of 0.98, again indicating excellent performance. We also found that the test showed good sensitivity to change in attentional functioning upon repeat testing in a subset of patients.

We now propose a new series of studies which will first develop the DelApp further, to make it easier to use, and then to test its performance in a group study and then a larger group of unselected patients. In contrast to our pilot studies, we will use separate researchers to assess the presence of delirium and to administer the DelApp. This is important to meet agreed standards for the evaluation of tests that could be used in clinical practice. As part of this project we will work with an industrial partner, Cambridge Cognition. This company is an international leader in computer-based cognitive testing and already supplies tests for dementia for the NHS.

Objectives:

(1) To further develop the DelApp, including optimisation of the test, user interface and data acquisition and display.

(2) To conduct studies in patients in general wards (delirium, dementia, control) and the intensive care units (delirium, control) to assess feasibility and diagnostic accuracy.

(3) To conduct further studies in unselected patients in general wards and the intensive care unit (delirium, dementia, control). The aim is to determine the diagnostic test accuracy of the DelApp in representative patient groups and clinical settings.

(4) To produce a software application which is suitable for use in clinical practice and which is commercially available.

Technical Summary

Delirium affects at least 1 in 8 acute hospital patients. It has multiple severe consequences, but is grossly under-detected.

A fundamental cause of the low rates of detection is the lack of well-validated tests for the core cognitive diagnostic feature of delirium: inattention. Currently available assessments of inattention have several drawbacks including inadequate discrimination between delirium and dementia, specific training required to administer, and lack of objectivity.

We previously developed a new neuropsychological test for the objective measurement of inattention in delirium. This was implemented on a purpose-built computerised device (Delbox). We have now developed a prototype software application (DelApp) for smartphones based on the same test.

The DelApp has many advantages over existing tests, including objectivity, automated scoring and ease-of-use. Studies in 30 hospital patients showed highly comparable performance between the Delbox and DelApp. Further proof-of-principle single-rater studies using the DelApp in more than 200 hospital patients have provided additional evidence of good performance of the DelApp.

The primary objectives of the programme of work are:

(1) To further develop the DelApp, including optimisation of test parameters, user interface and data acquisition and display.

(2) To conduct Phase 1/Phase 2 case-control studies in older patients (aged >64) in general wards (delirium, dementia, control groups) and in adult-age patients (aged >17) in intensive care units (delirium, control groups) to assess feasibility, reliability, diagnostic accuracy, and to inform optimal cut-points.

(3) To conduct a Phase 3 study in unselected patients in general wards and intensive care units. The main aim is to determine the diagnostic test accuracy and other test characteristics of the DelApp in detecting delirium in representative patient groups and clinical settings.

Planned Impact

Who might benefit from this research?

Several groups might benefit from this research.

Patients with delirium: less than two-thirds of delirium is detected.

Patients at risk of delirium: for example high risk elective surgical patients (eg. those with dementia) could be screened pre-operatively, and DelApp scores used as a baseline value to compare with post-operative values, using reductions in DelApp scores as a delirium marker.

Patients with dementia: two-thirds of hospitalised older patients with delirium also have dementia, and only half of that dementia is formally diagnosed. So delirium is a strong marker for dementia. Related to this is the fact that good care of dementia in hospitals and other institutions requires delirium detection and management, because delirium is an extremely frequent and harmful complication of dementia.

Hospital managers: delirium increases length of stay by 2-3 fold, and new institutionalisation risk by 3-5 fold. Delirium is also a risk factor for falls, dehydration, and other adverse outcomes. Because delirium affects at least 15% of patients (ie. >75 patients in a typical 500-bedded hospital), suboptimal management resulting from non-detection has important consequences in any hospital.

Policy-makers: increasing delirium detection rates is a critical part of improving the quality of care for older people in hospital. Recent reports such as the National Dementia Audit highlight that in NHS hospitals delirium is poorly detected.

Researchers: The DelApp provides a new tool for objective attentional assessment in delirium.

Cambridge Cognition or other companies who license the DelApp.

The above benefits could readily extend internationally, because the tests are not language-specific, though they do depend on basic knowledge of arithmetic.


How might they benefit?

Patients with delirium will benefit because detection and good management is associated with better outcomes for patients, including less distress. In the ICU, delirium is associated with a higher risk of future long-term cognitive impairment (eg. Pandharipande PP, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369:1306-16.). Detection of delirium linked with longer-term follow-up might allow patients with post-ICU cognitive impairment to have better support.

Delirium detection also provides a mechanism for improved dementia detection rates, in that older patients with delirium but with no prior diagnosis of dementia might be followed-up and assessed for dementia (after delirium recovery). Many hospitalised patients with delirium have established dementia, or are at high risk of future dementia (Davis DH, et al. Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study. Brain. 2012;135:2809-16).

Hospital managers and policy-makers would benefit from better delirium detection in multiple ways, including providing better quality of care in older people in hospital (via higher rates of delirium detection and consequent better care), and potentially reducing length of hospital stay and new institutionaliation.

Researchers might benefit through having better tools for assessment of inattention, with several benefits including increased comparability among studies and improved inter-rater reliability.

Companies such as Cambridge Cognition might benefit because the potential markets in the UK and internationally are large. Even if the initial use is focused on older patients in geriatrics wards, and ICUs, the numbers of patients (and associated healthcare) staff are considerable such that the DelApp is highly likely to be commercially viable.

More generally, given the enormous human and economic costs of delirium, methods that improve detection and thus care have the potential for considerable leverage, well beyond the costs of development and purchasing by end users or organisations.

Publications

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Description Project grant
Amount £260,000 (GBP)
Funding ID ARUK-PG2016B-12 
Organisation Alzheimer's Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2016 
End 10/2018
 
Title New computerised instrument for the assessment of attentional deficits in delirium 
Description A new computerised, programmable, battery-powered small device with new neuropsychological test protocols for delirium assessment in hospital inpatients. Validated. 
Type Of Material Technology assay or reagent 
Year Produced 2009 
Provided To Others? Yes  
Impact £150,000 grant from the MRC DPFS scheme to develop commercially-viable device, then £1M grant also from the MRC DPFS scheme (ongoing). 
 
Title New software application for the assessment of inattention as part of detecting delirium. 
Description A smartphone based test which is effective in detecting inattention as part of delirium. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2013 
Provided To Others? Yes  
Impact LUCID study of clonidine in delirium in Oslo - used as part of the delirium assessment. NIHR 4AT study (I am CI) - used as part of the delirium assessment. 
URL http://www.edinburghdelirium.ed.ac.uk/
 
Description DelApp studies - collaboration with Cambridge Cognition plc 
Organisation Cambridge Cognition Ltd
Country United Kingdom 
Sector Private 
PI Contribution We are engaging with this industrial partner to develop a potentially commercially-available smartphone application for delirium detection and monitoring.
Collaborator Contribution Cambridge Cognition are assisting by testing the DelApp for usability, and working with us on potential routes to market.
Impact No specific outputs at present (project ongoing).
Start Year 2013
 
Description Delirium epidemiology 
Organisation University of Cambridge
Department Cambridge Institute of Public Health
Country United Kingdom 
Sector Academic/University 
PI Contribution I have contributed to the generation of the idea to study delirium's impact on cognitive trajectories, interpretation of data, study design and writing of the manuscript
Collaborator Contribution Added knowledge on how delirium alters trajectories of cognitive decline and neuropathological findings.
Impact The main paper from the first set of analyses has been published in the journal Brain. The work directly led to the main author Daniel Davis gaining a Wellcome Trust Intermediate Fellowship. He is now based at the MRC Unit for Lifelong Health and Ageing in UCL. I maintain a very active collaboration - eg. as the senior author on Dr Davis's recent protocol paper describing the main study in his Wellcome Trust award.
Start Year 2010
 
Description Delirium epidemiology - Dr Daniel Davis 
Organisation University College London
Department MRC Unit for Lifelong Health and Ageing
Country United Kingdom 
Sector Public 
PI Contribution I worked closely with Daniel Davis to develop his application to the Wellcome Trust for an Intermediate Fellowship. He was successful in gaining this and has now taken up a position as WT IF at the MRC Unit for Lifelong Health and Ageing. I have contributed substantially to the ongoing conduct of Dr Davis's study including in study design, delirium ascertainment methods, and staff training (including on-site training in Edinburgh).
Collaborator Contribution Dr Davis is the lead scientist on this work and runs the study with involvement of a wider team.
Impact To date only the protocol paper has been published.
Start Year 2015
 
Description LUCID study 
Organisation University of Oslo
Country Norway 
Sector Academic/University 
PI Contribution I participated in the study design of 'The Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID'. This involved a visit to Oslo and correspondence after that regarding the protocol.
Collaborator Contribution Extensive involvement in developing the concept (partly stimulated by the results of our work on stress and delirium), the measurement of delirium, and other aspects of the protocol.
Impact Protocol for the study has been submitted for publication and now returned for revision with expected acceptance for publication. The study completed in 2017 and a manuscript will be submitted before May 2018
Start Year 2012
 
Description Neuropsychological testing in delirium 
Organisation University of Edinburgh
Department Psychology
Country United Kingdom 
Sector Academic/University 
PI Contribution Experimental design in neuropsychology of delirium projects
Collaborator Contribution Involvement in neuropsychology of delirium projects; consultation on cognitive test design, recruitment of dementia patients, statistical analyses
Impact New grant: 'Development of a new neuropsychological instrument for the diagnosis and monitoring of delirium'. This has led to new grants (£150,000 from the MRC Development Pathway Funding Scheme, then a further £1.06M from the same scheme). The device is known as the Delbox, and a software version called the DelApp. The project has so far multiple papers at international conferences and research papers. The DelBox and DelApp are being used in our own studies but also in other studies, eg. the LUCID study in Oslo, and a study in John Hopkins.
Start Year 2008
 
Title DelApp smartphone-based test for detection of inattention in delirium 
Description In negotiations with major medical devices company (turnover of several £B/yr) re purchase of US and EU patents for the DelApp, with a view to commercial use in clinical care. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2018
Development Status Actively seeking support
Impact Impacts yet to be realised but real prospect of adoption and commercial sale by major company. 
 
Title DelApp - smartphone-based software for assessment of inattention in delirium 
Description A new smartphone-based application which provides a brief test of attention useful for detecting delirium. Co-developed by the Edinburgh Delirium Research Group, and the NHS Medical Devices Unit (NHS Greater Glasgow and Clyde). 
Type Of Technology Software 
Year Produced 2014 
Impact The DelApp is being used in a study which is evaluating its performance formally. It is also being used in two other studies (NIHR 4AT study, and LUCID - clonidine in delirium study in Oslo). There have been several enquiries about use of the DelApp in studies and in clinical practice. A US patent application for the test has gone to grant and we expect a similar outcome for the EU application. 
URL http://www.edinburghdelirium.ed.ac.uk/
 
Description Keynote speaker, international conference (Australasian Delirium Association, Melbourne, 2018); debate on delirium screening at the same conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Keynote talk, Australasian Delirium Association on delirium treatment, and debated delirium screening. Presented data from the NIHR and MRC grants.
Year(s) Of Engagement Activity 2018
URL https://www.delirium.org.au/2018-Conference