Non-contact monitoring of agitation and use of a sheltering device in patients with dementia in emergency departments: a feasibility study

Background Agitation is common in geriatric patients with cognitive impairment, e.g. in persons with dementia (PWD), who are admitted to an emergency department (ED). It might be a first sign of upcoming delirium and is associated with a higher risk of an unfavorable clinical course. Hence, monitoring of vital signs and enhanced movement as indicators of upcoming agitation is essential in these patients during their stay in the ED. Since PWD rarely tolerate fixed monitoring devices, a novel developed non-contact monitoring system (NCMSys) might represent an appropriate alternative. Aim of this feasibility study was to test the validity of a NCMSys and of the tent-like “Charité Dome” (ChD), aimed to shelter PWD from the busy ED environment. Furthermore, effects of the ChD on wellbeing and agitation of PWD were investigated. Methods Both devices were attached to patient’s bed. Tests on technical validity and safety issues of NCMSys and ChD were performed at the iDoc institute with six healthy volunteers. A feasibility study evaluating the reliability of the NCMSys with and without the ChD was performed in the real-life setting of an ED and on a geriatric-gerontopsychiatric ward. 19 patients were included, ten males and nine females; mean age: 77.4 (55–93) years of which 14 were PWD. PWD inclusion criteria were age ≥ 55 years, a dementia diagnosis and a written consent (by patients or by a custodian). Exclusion criteria were acute life-threatening situations and a missing consent. Results Measurements of heart rate, changes in movement and sound emissions by the NCMSys were valid, whereas patient movements affected respiratory rate measurements. The ChD did not impact patients’ vital signs or movements in our study setting. However, 53% of the PWD (7/13) and most of the patients without dementia (4/5) benefited from its use regarding their agitation and overall wellbeing. Conclusions The results of this feasibility study encourage a future controlled clinical trial in geriatric ED patients, including PWD, to further evaluate if our concept of non-contact measurement of vital signs and movement combined with the “Charité Dome” helps to prevent upcoming agitation in this vulnerable patient group in the ED. Trial registration ICTRP: “Charité-Dome-Study - DRKS00014737” (retrospectively registered)

Schizophrenia, cannabis and neurotrophins

Immer mehr junge Menschen konsumieren Cannabis in manchmal hohen Dosierungen, wenn ihr Gehirn noch nicht voll entwickelt ist und besonders empfindlich auf äußere Einflüsse reagiert. Cannabis kann psychotische Zustände auslösen und verstärken, schizophrene Erkrankungen begünstigen. In einer prospektiven Studie wurden insgesamt 157 ersterkrankte, bisher unbehandelte schizophrene Patienten klinisch untersucht und in Abhängigkeit von früherem Cannabis- oder zusätzlichem Substanzkonsum in Gruppen unterteilt. „Signifikanter Cannabiskonsum“ wurde definiert als täglicher Konsum von mindestens 0.5 Gramm Cannabis über mindestens zwei Jahre, kein Konsum“ als weniger als fünf Ereignisse insgesamt. Hierbei zeigten die Patienten mit vorherigem regelmäßigen Cannabiskonsum ein signifikant jüngeres Ersterkrankungsalter, waren meistens männlich und zeigten häufiger das Bild einer paranoiden Schizophrenie als diejenigen ohne Substanzkonsum. Neben den klinischen Parametern wurden die Neurotrophine Nerve growth factor (NGF) und Brain- derived neurotrophic factor (BDNF) im Serum bestimmt, zwei Proteine, die für Entwicklung, Reifung und Funktionsaufrechterhaltung des ZNS essentiell sind. Diese Neurotrophine können, zumindest unter experimentellen Bedingungen, die Bluthirnschranke passieren und somit die Serumkonzentration potentiell die zentrale Neurotrophinkonzentration repräsentieren, die, gemäß der Entwicklungshypothese der Schizophrenie, bei Schizophrenien verändert sein kann. Chronischer Cannabiskonsum kann neurotoxisch wirken, wir postulierten eine zusätzliche Veränderung bei schizophrenen Patienten mit früherem Cannabiskonsum. In dieser Untersuchung zeigte sich eine signifikante Erhöhung des NGF-Serumwertes bei Schizophrenen mit vorangegangenem Cannabismissbrauch (12.5fach) und noch weitere signifikante Erhöhung bei Konsum von mindestens zwei weiteren Drogen (>100fach), die bei Schizophrenie ohne Cannabis, gesunden Kontrollen und Cannabiskontrollen ohne Schizophrenie nicht zu finden war. Es mussten also vulnerable Gehirne im Hinblick auf die Schizophrenie und der Substanzkonsum zusammentreffen, um die NGF-Erhöhung zu bewirken. Für BDNF zeigte sich ein ähnliches Bild. Waren die Patienten behandelt und weitgehend remittiert, gab es keine Gruppenunterschiede mehr. Die Ergebnisse bestätigten sich in einer prospektiven Untersuchung im Behandlungsverlauf, sodass wir die Hochregulation von NGF bzw. BDNF bei den Doppeldiagnosepatienten als endogenen „Reparaturmechanismus“ interpretierten. Diese Interpretation wurde unterstützt durch Ergebnisse einer unabhängigen Untersuchung alkoholerkrankter (nicht schizophrener) Patienten, die, solange keine kognitiven Einbussen vorhanden waren, signifikant erhöhte NGF-Serumwerte zeigten, die bei irreparabel geschädigten Korsakoff-Patienten nicht mehr nachweisbar waren. In einer folgenden vergleichenden Untersuchung der kognitiven Funktionen der schizophrenen Patienten mit und ohne chronischen Cannabiskonsum vor Krankheitsausbruch, die jetzt behandelt und weitgehend remittiert waren, schnitt die Gruppe Schizophrenie plus Cannabiskonsum zumindest nie schlechter ab als die Gruppe schizophrener Patienten ohne Cannabiskonsum. In einigen Tests zeigten erstere sogar signifikant bessere Ergebnisse, bei jedoch insgesamt kleiner Stichprobe. In einer Untersuchung des P50 Sensory Gating als Korrelat der bei Schizophrenie potentiell auftretenden Filterstörung zeigten die ansonsten gesunden chronischen Cannabiskonsumenten Veränderungen wie sie für unbehandelte Schizophrene typisch sind. Zwischen den behandelten schizophrenen Patienten mit und ohne Cannabiskonsum sowie den gesunden Kontrollen zeigten sich keine Unterschiede. Insgesamt ist damit der Effekt von Cannabis auf das für Schizophrenie vulnerable Gehirn, zumindest vor dem klinisch erkennbaren Krankheitsbeginn, bisher nicht abschließend zu bewerten. Neben den zweifellos ungünstigen Wirkungen wie früherem Ersterkrankungsalter, Reexazerbation der bereits behandelten Schizophrenie bei erneutem Cannabiskonsum, gibt es möglicherweise auch protektive Faktoren, die z. B. zur besseren Erhaltung der langfristigen kognitiven Leistungsfähigkeit beitragen.Many young people consume cannabis in high doses at a time when the brain is not yet fully developed and reacts very sensitive to external influences. Cannabis can induce and exacerbate psychosis and provoke schizophrenia. In a prospective study we investigated 157 drug-naive first-episode schizophrenic patients and grouped them according to previous cannabis consumptionor additional drug consumption. Significant Cannabis consumption was defined as a daily intake of at least 0.5 gram of Cannabis for at least two years, no consumption as five times or less in a lifetime. As a result patients with previous regular cannabis consumption were significantly younger at disease onset, were mostly male and showed predominantly paranoid schozophrenia compared to those without substance abuse. Apart from clinical parameters we measured the neurotrophins NFG and BDNF in serum. Those two proteins are essentiel for the development, maturation and maintenance of function of the CNS. At least in experimental conditions they can pass the blood-brain barrier and thus their serum concentration might represent the central neurotrophin concentration that might be altered according to the developmental hypothesis of schizophrenia. Chronic Cannabis consumption can be neurotoxic and we postulated additional changes in schizophrenic patients with previous cannabis consumption. In our investigation schizophrenics with previous cannabis abuse showed a significant increase of serum-NGF concentrations (12.5 fold), even more so when at least two additional substances were consumed (>100fold). Schizophrenics without cannabis, healthy controls and cannabis controls showed no such changes. Thus, the two factors vulnerable brain and cannabis or additional substance abuse had to meet in order to result in increased serum- NGF. For BDNF the results were similar. When the patients were treated and remitted there were no more group differences. Those results were replicated in a further prospective study. We thus interpreted the up-regulation of NGF and BDNF in the dual diagnosis patients as endogenous repair mechanism. This interpretation was supported by a study with non-schizophrenic alcohol- dependent patients who showed increased NGF serum values as long as no cognitive changes had occurred. Korsakoff patients showed no more increase. A following investigation compared the cognitive function of treated schizophrenic patients with and without previous cannabis abuse. The previously cannabis abusing schizophrenic patients never showed inferior results to the non-abusers, in some tests they were even significantly better. In an investigation about P50 sensory gating the non-schizophrenic cannabis abusers showed changes typical for schizophrenia, this was in contrast to the (treated) schizophrenic patients and normal controls. All in all the effect of cannabis on the brain vulnerable to schizophrenia is not completely understood, at least when the chronic cannabis consumption precedes schizophrenia. Apart from unfavourable effects like younger age at disease onset and reexacerbation with further cannabis consumption there may be protective factors contributing to the preservation of cognitive function in schizophrenia

Auditory mismatch negativity and repetition suppression deficits in schizophrenia explained by irregular computation of prediction error.

BACKGROUND:The predictive coding model is rapidly gaining attention in schizophrenia research. It posits the neuronal computation of residual variance ('prediction error') between sensory information and top-down expectation through multiple hierarchical levels. Event-related potentials (ERP) reflect cortical processing stages that are increasingly interpreted in the light of the predictive coding hypothesis. Both mismatch negativity (MMN) and repetition suppression (RS) measures are considered a prediction error correlates based on error detection and error minimization, respectively. METHODS:Twenty-five schizophrenia patients and 25 healthy controls completed auditory tasks designed to elicit MMN and RS responses that were investigated using repeated measures models and strong spatio-temporal a priori hypothesis based on previous research. Separate correlations were performed for controls and schizophrenia patients, using age and clinical variables as covariates. RESULTS:MMN and RS deficits were largely replicated in our sample of schizophrenia patients. Moreover, MMN and RS measures were strongly correlated in healthy controls, while no correlation was found in schizophrenia patients. Single-trial analyses indicated significantly lower signal-to-noise ratio during prediction error computation in schizophrenia. CONCLUSIONS:This study provides evidence that auditory ERP components relevant for schizophrenia research can be reconciled in the light of the predictive coding framework. The lack of any correlation between the investigated measures in schizophrenia patients suggests a disruption of predictive coding mechanisms in general. More specifically, these results suggest that schizophrenia is associated with an irregular computation of residual variance between sensory input and top-down models, i.e. prediction error

Scatterplots of mismatch negativity (MMN) and repetition suppression measures of P50, N100, and P200.

<p>Both MMN and repetition suppression measures are conceptualized as event-related components that signal the difference between predicted and unexpected stimuli (i.e. prediction error). String correlations are therefore expected, which are present in healthy controls (grey dots), but absent in schizophrenia patients (black dots).</p

Demographic and clinical variables as mean ± SD (range).

<p>Demographic and clinical variables as mean ± SD (range).</p

Grand averaged event-related potential waveforms elicited by auditory click-conditioning stimuli for healthy controls (blue line) and schizophrenia patients (green line) pooled across electrodes Fz and Cz.

<p>Onset of stimuli is at 0 ms (first click, solid line) and at 500 ms (second click, dashed line). Click-conditioning stimuli evoke a P50 component (A) and a N100/P200 component complex (B). Topographic maps are given for the maximum amplitude of the P50, N100 and P200 amplitude elicited by the first click stimuli for both groups.</p

Grand averaged auditory evoked responses of healthy controls (blue) and schizophrenia patients (green) pooled across electrodes Fz and Cz.

<p>Stimulus onset at 0 ms. (A) Event-related responses to deviant (solid lines) and to standard stimuli (dotted lines) stratified by group. (B) Difference waveforms (deviant minus standard) with a clear mismatch negativity component between 100 and 200 ms. Topographic maps are given for the maximum amplitude of the MMN for both groups.</p