Adaptable healing patient room for stroke patients. A staff evaluation.

INTRODUCTION: This article is part of the focus theme of Methods of Information in Medicine on "Pervasive Intelligent Technologies for Health". BACKGROUND: This paper addresses the evaluation with hospital staff of an in-patient environment that supports patients, family, nursing staff and medical specialists during the recovery process of neurology patients and especially patients recovering from a stroke. We describe the methods that were used to evaluate the Adaptive Daily Rhythm Atmospheres (ADRA), Artificial Skylight (AS) and Adaptive Stimulus Dosage (ASD) concepts. OBJECTIVES: The goal of this evaluation was to gather qualitative and quantitative feedback from hospital staff about the usefulness, the usability and desirability of the Adaptive Daily Rhythm Atmospheres (ADRA), Artificial Skylight (AS) and Adaptive Stimulus Dosage (ASD) concepts that were implemented as different phases of a novel healing patient room. This paper reports the effects of these concepts with regard to 1) the healing process of the patient and 2) the workflow of the staff. These results are part of a larger R&D project and provide the initial feedback in an iterative user-centered design methodology. METHODS: After signing informed consents, the group of participants was taken to the laboratory environment where they were introduced to the Adaptive Healing Environment Patient Room and where they could also experience the room. Then, the participants were seated next to the patient bed so they had a similar viewing angle as the patients. The participants received a booklet with questionnaires. The items on this questionnaire addressed the influence on the healing process (i.e., the possible effect the concept/phase has on the healing process of the patient, meaning faster recovery, better sleep and enhanced well-being) and influence on the workflow (i.e., the possible effect of such a concept/phase on the working activities of the staff in the ward). We presented every concept (AS and ASD) and all the phases of ADRA. After every presentation of the concept or phase of the ADRA system the participants rated the concept or phase anonymously on a 7-point Likert scale. In addition to rating the phase in the therefore designed booklets, they were also asked to motivate their ratings in writing. Subsequently, a focus group discussion took place. During the discussion the two note takers wrote down all the comments. Afterwards the quantitative results were analyzed with the non-parametric Kruskal-Wallis test. Significant effects were further analyzed in a post-hoc Mann-Whitney test. RESULTS: The results show that hospital staff expects a positive effect on the healing process of the patient for the Artificial Skylight, the Adaptable Stimulus Dosage concept and the different ADRA phases that provide a clear daily rhythm structure during the day. In fact the staff members from different healthcare institutions and with different professional roles agreed on most aspects. In addition, the staff also expected a positive effect for almost all phases on the efficiency of the clinical workflow, also for the AS and ASD concepts. This is a very promising result as the phases were designed primarily with the healing effect of the patient in mind. CONCLUSIONS: The hospital staff evaluation in the laboratory setting gave us an indication of the likely impact of the Adaptive Healing Environment Patient Room on the healing progress of patients. Furthermore, this laboratory evaluation of the concepts was an important step that enabled to improve the shortcomings of the current concept before starting clinical trials. In addition, we generated feedback from different departments from different institutions, which suggest that they all see similar added values for the patient room.

Infusion of flesinoxan into the amygdala blocks the fear-potentiated startle.

In a previous study it was demonstrated that flesinoxan, a selective serotonin (5-HT)1A receptor agonist, had anxiolytic properties in the fear-potentiated startle paradigm. The present study investigated the putative site of action of flesinoxan in this paradigm. Flesinoxan infused either into the dorsal raphe nucleus or the median raphe nucleus did not affect startle potentiation. Bilateral infusion of flesinoxan into the central nucleus of the amygdala on the other hand, dose-dependently blocked the fear-potentiated startle response. These data indicate that flesinoxan exerts it anxiolytic effects in the fear-potentiated startle paradigm via the central nucleus of the amygdala, whereas the dorsal and median raphe nuclei are not directly involved in this process.

The anxiolytic effect on the fear-potentiated startle is not due to a non-specific disruption.

In the present study, the effects of alprazolam, chlordiazepoxide, ethanol and haloperidol in the strychnine-potentiated startle response paradigm were investigated. Because strychnine increases control startle levels without fear-conditioning, no central state of fear exists. When anxiolytic drugs reduce the fear-induced potentiation of the startle response without reducing the strychnine-induced startle potentiation, their attenuating effect on startle potentiation in the fear-potentiated startle response paradigm can more likely be attributed to their anxiolytic properties. The selected drugs, which effectively reduced the fear-induced startle potentiation in an earlier study, indeed did not selectively affect the strychnine-induced startle potentiation, supporting the notion that the dose-dependent reduction of startle potentiation due to anxiolytic drugs in the fear-potentiated startle response paradigm does not reflect a "non-specific" disruption of startle behavior.

The effects of 5-HT1A receptor agonists, 5-HT1A receptor antagonists and their interaction on the fear-potentiated startle response.

The present study investigated whether the anxiolytic effect of 5-HT1A receptor agonists on the fear-potentiated startle response could be antagonized by 5-HT1A receptor antagonists. Therefore, control and fear-potentiated startle amplitudes were measured after co-administration of vehicle, flesinoxan (10 mg/kg PO) or 8-OH-DPAT (0.3 mg/kg SC) and DU 125,530 (0, 1, 3 and 10 mg/kg SC), (+/-)-pindolol (0, 3, 10 and 30 mg/kg SC) or WAY 100,635 (0, 0.1, 0.3 and 1 mg/kg SC). Unexpectedly, the three antagonists themselves as measured in the vehicle-pretreatment groups dose-dependently decreased startle potentiation. Further, DU 125,530 and WAY 100,635 were able to reverse the attenuating effect of 8-OH-DPAT, while no antagonism of the flesinoxan effect on startle potentiation was found. In contrast, both the flesinoxan- and 8-OH-DPAT-induced lower lip retraction were antagonized by DU 125,530 and WAY 100,635, but not by (+/-)-pindolol. The findings of the present study suggest that drugs acting on 5-HT1A receptors differentially affect lower lip retraction and startle potentiation probably mediated by different neuronal populations.

Effects of 5-HT1A receptor ligands in a modified Geller-Seifter conflict model in the rat.

In a modified Geller-Seifter conflict procedure, rats were trained to lever-press for food under a multiple variable interval-fixed ratio (VI30: food; FR10: food + shock) schedule of reinforcement. The ability to antagonize response suppression in the punished period is considered a good predictor for anxiolytic activity. Chlordiazepoxide and alprazolam increased punished responding. The 5-HT1A receptor agonists flesinoxan (R(+)-N-[2[4-(2,3-dihydro-2-2-hydroxymethyl-1,4-benzodioxin-5-yl)- 1-piperazinyl]ethyl]-4-fluorobenzoamide; 0.1-10.0 mg/kg) and 8-OH-DPAT (8-hydroxy-2-(di-n-propyl-amino)tetralin; 0.03-0.5 mg/kg) significantly increased punished responding, supporting a role of the 5-HT1A receptor in anxiety. 8-OH-DPAT and flesinoxan also reduced unpunished responding. The anxiolytic effects of 8-OH-DPAT and flesinoxan could only be antagonized with a high dose (1.0 and 3.0 mg/kg respectively) of the 5-HT1A receptor antagonist WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride). All doses of WAY-100635 antagonized the 5-HT1A-induced effects on unpunished responding. The dissimilarity in dose-response curve of WAY-100635 on punished and unpunished behaviour poses questions about the mediation of these effects.

Control conditions in the fear-potentiated startle response paradigm.

In the present study, the fear-potentiated startle response paradigm was modified in order to investigate the decrease in control startle levels often observed after administration of anxiolytic drugs. The within-animal comparison of control startle amplitudes and fear-potentiated startle amplitudes normally used was replaced by a between-animal comparison. Moreover, the experimental design was extended with an additional control group, a no-shock group. The anxiolytics diazepam and chlordiazepoxide were used as pharmacological tools. The main findings were that both benzodiazepines dose-dependently reduced control startle amplitudes and no-shock startle amplitudes equally, suggesting that shock-associated contextual cues are not responsible for the drug-induced decrease in control startle amplitudes in the fear-potentiated startle response paradigm.

Fear-potentiated startle response is remarkably similar in two laboratories.

The fear-potentiated startle response paradigm is used to investigate anxiolytic properties of drugs. The first objective of the present study was to further investigate the predictive validity of this paradigm. The anxiolytics chlordiazepoxide (2.5-10 mg/ kg IP) and oxazepam (1-10 mg/kg PO) and the putative anxiolytic flesinoxan (1-10 mg/kg PO) decreased startle potentiation dose-dependently, indicating an anxiolytic effect. The antidepressant fluvoxamine (5-20 mg/kg PO) did not affect startle potentiation. Ideally, anxiolytic drugs attenuate startle potentiation without affecting control startle levels, although some studies report altered control startle amplitudes. The second objective was to investigate whether different effects on control startle amplitudes are related to different startle devices. Therefore, the drugs were tested in two laboratories. Results showed no significant differences between laboratories, indicating that equipment is not a critical factor in the drug-induced alteration of control startle levels. In an additional experiment, it was shown that flesinoxan (10 mg/kg PO) did not affect strychnine-induced startle potentiation, supporting the idea that the attenuating effect of flesinoxan on the fear-potentiated startle response is due to its anxiolytic properties. Thus, the fear-potentiated startle response paradigm appears a valid and reliable model for anxiolytic properties of drugs.

Predictive validity of the potentiated startle response as a behavioral model for anxiolytic drugs.

The fear-potentiated startle (PSR) paradigm is a putative behavioral model for the determination of anxiolytic properties of drugs. The present study further investigated the predictive validity of the model. Predictive validity is high, when only drugs clinically used as anxiolytics attenuate PSR dose dependently. Results showed that startle potentiation decreased dose dependently after the administration of the anxiolytics CDP (2.5-10 mg/kg, IP) and alprazolam (1-3 mg/kg, IP). After administration of the clinically non-anxiolytic drugs amitriptyline (2.5-10 mg/kg, IP), carbamazepine (5-20 mg/kg, IP), fentanyl (0.0025-0.04 mg/kg, SC), naloxone (2.5-10 mg/kg, IP), nicotine (0.4-1.6 mg/kg, IP), alcohol (500-2000 mg/kg, IP), and d-amphetamine (0.6-2.4 mg/kg, IP), a dose-dependent decrease in startle potentiation was not found. The PSR correctly discriminated most of the drugs tested in clinically anxiolytic and clinically non-anxiolytic drugs. However, haloperidol behaved as a false positive, and results of nicotine and alcohol were at variance with results reported by others.