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.

Development and feasibility of a smartphone-based test for the objective detection and monitoring of attention impairments in delirium in the ICU.

PURPOSE: Delirium in the ICU is under-diagnosed. We evaluated feasibility and performance of a novel smartphone-based test for objectively detecting inattention in delirium. MATERIAL AND METHODS: DelApp-ICU combines a behavioural assessment and an attention task, whereby participants follow simple commands and count serially presented circles (score range 0-12, lower scores indicating worse performance). We assessed feasibility through staff interviews. Then we performed a preliminary case-control study in patients with and without delirium (ascertained with the Confusion Assessment Method for the ICU) who underwent the DelApp-ICU on up to 4 days. RESULTS: Forty-six patients (median age = 57.5 years, range 18-83) were assessed 89 times in total (N's = 46, 29, 10 and 4 for subsequent assessments; 33.7% delirious). DelApp-ICU scores were lower in delirium (N = 20; median = 0.5, Inter-Quartile Range (IQR) = 0-4.75) compared to no delirium (N = 26, median = 12, IQR = 8-12) on days 1, 2 and 3 (p < 0.001, p < 0.001 and p < 0.05, respectively). A DelApp-ICU score ≤6 was 100% sensitive and 96% specific to delirium on day 1. Positive and Negative Predictive Values were 91% and 100%, respectively. DelApp-ICU scores were responsive to changes in CAM-ICU status. CONCLUSIONS: DelApp-ICU shows promise for assessing inattention and delirium in ICU patients, including longitudinally monitoring deficits and providing a metric of delirium severity.

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.

Pre-clinical investigations of multi-path propagation in transcranial Doppler ultrasound flow phantom.

There are various practical situations in medical applications when pre-clinical investigations must be performed using a simulation environment or test bench prior to human studies. One example is the analysis of propagation channels in Transcanial Doppler (TCD) ultrasound (US), a signal processing challenge requiring the analysis of data from US waves scattered in three dimensions (3D). When examining the effects of scatterers in such channels, it is common to use a data acquisition test bench and a Doppler flow phantom. Such medical phantoms are frequently required to verify image and signal processing systems, and are often used to support algorithm development for a wide range of imaging and blood flow assessments. In this paper we describe a TCD simulation environment for the acquisition, investigation and pre-clinical data analysis of multi-path propagation in TCD US systems. This is demonstrated by comparing the anticipated theoretical and simulation channel statistics with the measured acoustic characteristics in terms of the probability distribution and autocorrelation functions.

Development of a smartphone application for the objective detection of attentional deficits in delirium.

BACKGROUND: Delirium is an acute, severe deterioration in mental functioning. Inattention is the core feature, yet there are few objective methods for assessing attentional deficits in delirium. We previously developed a novel, graded test for objectively detecting inattention in delirium, implemented on a computerized device (Edinburgh Delirium Test Box (EDTB)). Although the EDTB is effective, tests on universally available devices have potential for greater impact. Here we assessed feasibility and validity of the DelApp, a smartphone application based on the EDTB. METHODS: This was a preliminary case-control study in hospital inpatients (aged 60-96 years) with delirium (N = 50), dementia (N = 52), or no cognitive impairment (N = 54) who performed the DelApp assessment, which comprises an arousal assessment followed by counting of lights presented serially. Delirium was assessed using the Confusion Assessment Method and Delirium Rating Scale-Revised-98 (DRS-R98), and cognition with conventional tests of attention (e.g. digit span) and the short Orientation-Memory-Concentration Test (OMCT). RESULTS: DelApp scores (maximum score = 10) were lower in delirium (scores (median(IQR)): 6 (4-7)) compared to dementia (10 (9-10)) and control groups (10 (10-10), p-values < 0.001). Receiver operating characteristic (ROC) analyses revealed excellent accuracy of the DelApp for discriminating delirium from dementia (AUC = 0.93), and delirium from controls (AUC = 0.99, p-values < 0.001). DelApp and DRS-R98 severity scores were moderately well correlated (Kendall's tau = -0.60, p < 0.001). OMCT scores did not differ between delirium and dementia. CONCLUSIONS: The DelApp test showed good performance, supporting the utility of objectively measuring attention in delirium assessment. This study provides evidence of the feasibility of using a smartphone test for attentional assessment in hospital inpatients with possible delirium, with potential applications in research and clinical practice.

A wall-less poly(vinyl alcohol) cryogel flow phantom with accurate scattering properties for transcranial Doppler ultrasound propagation channels analysis.

Medical phantoms are frequently required to verify image and signal processing systems, and are often used to support algorithm development for a wide range of imaging and blood flow assessments. A phantom with accurate scattering properties is a crucial requirement when assessing the effects of multi-path propagation channels during the development of complex signal processing techniques for Transcranial Doppler (TCD) ultrasound. The simulation of physiological blood flow in a phantom with tissue and blood equivalence can be achieved using a variety of techniques. In this paper, poly (vinyl alcohol) cryogel (PVA-C) tissue mimicking material (TMM) is evaluated in conjunction with a number of potential scattering agents. The acoustic properties of the TMMs are assessed and an acoustic velocity of 1524ms(-1), an attenuation coefficient of (0:49) × 10(-4)fdBm(1)Hz(-1), a characteristic impedance of (1.72) × 10(6)Kgm(-2)s(-1) and a backscatter coefficient of (1.12) × 10(-28)f(4)m(-1)Hz(-4)sr(-1) were achieved using 4 freeze-thaw cycles and an aluminium oxide (Al(2)O(3)) scattering agent. This TMM was used to make an anatomically realistic wall-less flow phantom for studying the effects of multipath propagation in TCD ultrasound.

Idiopathic, isolated fovea plana with bilateral off-centre multifocal ERGs.

BACKGROUND: The purpose of this paper is to report a case of idiopathic isolated fovea plana showing asymmetry in the multifocal electroretinogram (mfERG). METHODS: We carried out optical coherence tomography (OCT) imaging, macular pigment density measurement, genetic testing and electrophysiological testing with visual evoked potentials and mfERGs on a young, highly myopic female of Pakistani origin, who had good visual acuity and no nystagmus. RESULTS: OCT imaging revealed a complete absence of any foveal pit in either eye. Macular pigment density was normal and visual evoked potentials indicated normal chiasmal crossings, excluding albinism. Genetic testing revealed normal PAX6 coding data, excluding aniridia as a cause. mfERGs showed asymmetry consistent with off-centre fixation to the temporal side of the fovea in both eyes, but were otherwise normal. CONCLUSION: Lack of a foveal pit is a well-known finding in conditions such as oculocutaneous albinism and PAX6 gene-related aniridia. Isolated fovea plana is less common, and this case illustrates that the absence of a foveal pit does not necessarily result in a poor visual outcome. The finding of asymmetry in the mfERG in such a case is novel, and may indicate a functional adaptation to the structure of the fovea.

Binasal visual field defects are not specific to vigabatrin.

This study investigated the visual defects associated with the antiepileptic drug vigabatrin (VGB). Two hundred four people with epilepsy were grouped on the basis of antiepileptic drug therapy (current, previous, or no exposure to VGB). Groups were matched with respect to age, gender, and seizure frequency. All patients underwent objective assessment of electrophysiological function (wide-field multifocal electroretinography) and conventional visual field testing (static perimetry). Bilateral visual field constriction was observed in 59% of patients currently taking VGB, 43% of patients who previously took VGB, and 24% of patients with no exposure to VGB. Assessment of retinal function revealed abnormal responses in 48% of current VGB users and 22% of prior VGB users, but in none of the patients without previous exposure to VGB. Bilateral visual field abnormalities are common in the treated epilepsy population, irrespective of drug history. Assessment by conventional static perimetry may neither be sufficiently sensitive nor specific to reliably identify retinal toxicity associated with VGB.

Simultaneous structural and functional imaging of the macula using combined optical coherence tomography ophthalmoscope and multifocal electroretinogram.

Multimodal imaging (MMI) is a new imaging technique that combines an electrophysiological test (multifocal electroretinogram) with an optical coherence tomography ophthalmoscope. MMI allows the two technologies to operate simultaneously yet independently to provide accurate correlation of macular structure and function at multiple sites. Preliminary work with MMI in patients with macular holes showed that functional deficits existed beyond the geographical area of structural alterations and that macular hole size did not always correlate with the severity of functional loss. Functional information may therefore be important when assessing prognosis in these patients. We envisage that MMI may prove a useful new tool in the assessment of many macular pathologies.

Vitamin A deficiency modifies the mfERG: a case study of rod influence on the mfERG.

We report an observational case study which showed that the rod pathway may have a significant effect on the multifocal electroretinogram (mfERG). A 68-year-old lady diagnosed with Vitamin A deficiency underwent standard ERG and mfERG. ERG rod and cone function were analysed and the first order mfERG responses were determined. At presentation, there was no demonstrable rod function on ERG testing and normal cone function. mfERG P1 amplitude responses were normal but mfERG P1 latency responses were significantly delayed. Four weeks after initiating treatment with intramuscular Vitamin A, ERG rod function significantly improved. However, cone amplitude was reduced and the 30 Hz flicker latencies decreased. Furthermore, mfERG P1 latency returned to normal and interestingly mfERG P1 amplitude responses showed a significant reduction. These results alter our understanding of the mfERG response by indicating that there is a possible inhibitory influence on mfERG responses from rod pathway systems.

Wide field multifocal and standard full field electroretinographic features of hemi retinal vein occlusion.

The purpose of this study was to document the standard full field electroretinographic (ERG) and wide field multifocal electroretinographic (WF-mfERG) findings in eyes with recent onset hemi-retinal vein occlusion (HRVO) and to compare the electro-diagnostic findings in the affected and fellow eyes with reference to normative data. Eight patients with HRVO were assessed using ERG and WF-mfERG. WF-mfERG first order responses from the affected hemi-retinae and the unaffected hemi-retinae in each affected eye were compared. WF-mfERG responses from each affected hemi-retina and from the symmetrical hemi-retina of each fellow eye were compared. ERG responses between affected and unaffected eyes were also compared. All electrodiagnostic tests were compared to normative data (5-95% confidence limits derived from age-related controls). WF-mfERG P1 and N1 implicit times were greater for the affected hemi-retinae than for the unaffected hemi-retinae (p <0.05). WF-mfERG N1 and P1 implicit times were prolonged (p < 0.05) and WF-mfERG P1/N1 amplitude ratios were significantly reduced (p < 0.05) for the affected eyes when compared with the fellow eyes. Maximal b-wave, cone b-wave and flicker implicit times were prolonged (p < 0.05) when comparing affected and fellow eyes. These results indicate that retinal injury due to HRVO culminates in significant delay of both ERG and WF-mfERG implicit times. These results suggest that WF-mfERG in combination with ERG may have a role in the management of HRVO.

Multifocal electroretinographic features of central retinal vein occlusion.

PURPOSE: To determine the features of wide-field multifocal electroretinography (WF-mfERG) recorded in patients with central retinal vein occlusion (CRVO) and to compare WF-mfERG responses of the affected and fellow eyes. In addition, WF-mfERG responses were also compared by using standard electroretinography (ERG). METHODS: WF-mfERG and ERG responses were recorded from both eyes of 56 patients with CRVO. The WF-mfERG responses, obtained using a custom-built system were grouped into central and peripheral rings. The P1 amplitudes, and P1 and N1 implicit times were grouped and averaged within both rings. Nonparametric statistical analysis was used to compare the ERG results from the affected and fellow eyes. The results were also compared with normative data (5% to 95% confidence limits). RESULTS: CRVO markedly affected all the parameters of the WF-mfERG. In the affected eyes, 98% of the central and 91% of the peripheral P1 implicit times fell outside the normal range, as opposed to 35% of the 30-Hz flicker implicit times. The WF-mfERG responses obtained from eyes with CRVO were significantly different (P<0.01) from those derived from the fellow eye. The central and peripheral P1 implicit times were also abnormal in 59.2% and 46.9% of the fellow eyes, respectively. CONCLUSIONS: WF-mfERG is more susceptible than the standard ERG to changes in the nonlinear dynamics of the eye due to the multiple frequencies of stimulation used to record WF-mfERG responses. WF-mfERG could be a sensitive indicator of the underlying disease affecting the retina in eyes with CRVO and may have a role in the clinical setting.

The multifocal ERG: unmasked by selective cross-correlation.

The purpose of this paper is to provide the reader with a better insight into the mechanisms of multifocal ERG (mfERG) recording. The construction of the first and second order mfERG responses were examined by recovering the response to specific pulse trains embedded in the m-sequence.A custom built pc based multifocal system driving a LED stimulator was used to record a 61 element mfERG and a global ERG. The global ERG recording was used to enable the recovery of different pulse trains embedded in the m-sequence. Summation of these individual pulse trains was performed and the results compared with the standard full cross-correlation. An isolated pulse response is defined as a flash of light that has no other flashes within two m-sequence base periods before or after the flash. This isolated pulse response was recovered from the raw data and this response input into a simple superposition model to predict the waveform shape for specific pulse trains. The superposition model was compared with the actual selective cross-correlation for a particular pulse train. The summations of the selective cross-correlation components give identical responses to the full cross-correlation. The superposition model also predicts the waveform shapes recovered by the selective cross-correlation procedure. The mfERG response is a complex composite response from a number of different pulse trains. Examination of the individual waveform shapes provides some insight into the origin of the mfERG waveform. The main contributions to the P1 component are the same as for an isolated response and as with the standard ERG this component is likely to be dominated by the mid retina. The N1 component is also likely to have similar origins to that of the isolated response but the amplitude is dominated by contributions from pulse trains where there is no change of state and therefore includes a component from the interaction between two consecutive stimuli. The N2 component is a composite response dominated by the interaction between two successive stimuli two base periods apart and the P1 component of a second stimulus delayed one frame from the first stimulus.

Repeatability and reproducibility of corneal thickness measurements by optical coherence tomography.

PURPOSE: To assess the repeatability and interoperator and intersession reproducibility of central corneal thickness (CCT) measurements made by a commercially available optical coherence tomography (OCT) system. METHODS: Intersession and interoperator reproducibility and repeatability were defined according to the guidelines of the British Standards Institution and examined in a control group of 14 normal subjects. An in-house computer program was used to evaluate central corneal thickness from these scans. RESULTS: The coefficient of interoperator reproducibility was 0.18%, whereas that for intersession reproducibility was 1.11%. Wilcoxon analysis (5% level of significance) showed that there was no statistically significant difference between scans acquired during different sessions or by different operators. Coefficients of repeatability were all less than 3%. The average CCT was 526 +/- 28 microm (SD) and the range of normal CCT between 5th and 95th percentiles was 498 to 576 microm. CONCLUSIONS: Although the commercially available OCT scanner was designed for retinal imaging, with a few minor modifications, the system may be used to image the anterior segment. Previous studies have shown that OCT measurements correlate well with those from conventional techniques, and it has the added advantage of being a noncontact technique. This study further demonstrates that the OCT measurements show a high degree of repeatability and reproducibility. Thus, OCT is emerging as a promising tool for evaluation of CCT in the clinical setting.

Repeatability and reproducibility of macular thickness measurements with the Humphrey OCT system.

PURPOSE: To assess the accuracy, precision, repeatability, and reproducibility of measurements made by the Humphrey optical coherence tomography (OCT) system (Humphrey-Zeiss Medical Systems, San Leandro, CA). METHODS: The performance of the system was first investigated by scanning a test object containing an air gap of known size. Measurements were repeated with water or glycerin in the gap. In the clinical setting, macular thickness measurements were obtained from a control group of 20 normal subjects. For analysis, these scans were divided into eight sections, each containing 10 A-scans. RESULTS: The average gap thickness was found to be close to the true value in all cases. The overall coefficients of intersession reproducibility were less than 1% for the test object and 1.51% for the control group. There was no significant difference between scans acquired during different sessions. The overall coefficients of repeatability for the test object were between 0.2% and 1.1% and between 1% and 2% for the control group. The range of normal retinal thickness in terms of the 5th and 95th percentiles was 222 to 248 microm in women and 234 to 257 microm in men. CONCLUSIONS: Measurements made from OCT scans were found to be accurate and precise. Introducing water or glycerin into the test object resulted in considerable degradation of the signal, but measurements of gap thickness were still shown to be accurate, precise, reproducible, and repeatable. Retinal thickness measurements in the macular area were repeatable and reproducible. This demonstrates that OCT is a useful tool in the monitoring of patients with conditions that affect macular thickness, even when there is considerable degradation of the OCT signal.