Assessment of Dopamine and Serotonin Release in the Non-Human Primate Brain using PET

The molecular imaging technique positron emission tomography (PET) allows for non-invasive examination of biochemical markers in the living brain. For over three decades PET studies have provided important insight into the relationship of monoaminergic neurotransmitter systems to brain functioning and psychiatric disorders. A more recent application of PET is the study of endogenous neurotransmitter release in vivo. Clinical relevance of such methods is found in studies demonstrating enhanced amphetamine-induced dopamine release in schizophrenia patients, whereas PET studies in non-human primates provide a translational model for evaluation of the pharmacological mechanisms before initiation of studies in man. The first aim of this thesis was to develop improved methods for measurement of endogenous dopamine levels. In study I the potent D2/D3 receptors agonist (R)-(-)-2-methoxy-N-n-propyl-norapomorphine (MNPA) was radiolabeled with carbon-11 and found suitable for in vivo characterization of the high affinity state. In study II, amphetamine-induced displacement of [11C]MNPA binding by dopamine was ~1.8 fold higher at four different doses than for the antagonist [11C]raclopride and demonstrated that an agonist radioligand has improved sensitivity to endogenous neurotransmitter level. Study III aimed to further obtain in vivo support for the existence of two affinity states for the D2/D3 receptors. Receptor occupancy of the exogenous agonist apomorphine was determined with [11C]MNPA and [11C]raclopride. Binding of [11C]MNPA and [11C]raclopride was inhibited monophasic and approached full saturation. ID50 and Ki values of apomorphine were indistinguishable when measured with the agonist or antagonist radioligand. Study III did not support the existence of two affinity states and a possible explanation could be that all D2/D3 receptors are in the high affinity state in vivo. In study IV, the new D1/D5 receptors partial agonist radioligand (S)-[11C]N-methyl-NNC 01-0259 was found insensitive to dopamine levels, and receptor binding was inferior to previously developed antagonist radioligands. Moreover, a COMT formed radiometabolite was found to enter the brain but the formation could be prevented with the use of a COMT inhibitor. COMT inhibition provides a methodology enabling quantitative PET measurements with (S)-[11C]N-methyl-NNC 01-0259. The second aim of this thesis was to evaluate the sensitivity of the new 5-HT1B receptor radioligand [11C]AZ10419369 to alterations in endogenous serotonin concentration. Previous serotonergic PET radioligands have ambiguously shown sensitivity to serotonin level. In study V the effective serotonin releaser fenfluramine decreased the binding of [11C]AZ10419369 in a dose-dependent manner. In study VI the effect of fenfluramine on [11C]AZ10419369 binding was confirmed using an equilibrium approach with a bolus infusion protocol. The further developed methodology is suitable for exploring the sensitivity limit to serotonin levels as measured using [11C]AZ10419369 and PET. In conclusion, the present thesis demonstrates that the D2/D3 receptors agonist radioligand [11C]MNPA is an improvement for measurement of dopamine release, when compared to previously used antagonist radioligands. Moreover, a novel methodology, using the 5-HT1B receptor antagonist [11C]AZ10419369 and PET, was developed for measurement of serotonin release in the living brain. These newly developed methodologies may help to further understand the treatment and pathophysiology of several major neurological and psychiatric disorders

Nurses' perceptions in caring for people with dementia in Dutch acute hospitals

AIMS AND OBJECTIVES: Overall, this study aimed to describe nursing care for patients with dementia in acute hospitals, with the objectives of describing the provided nursing care (a), nurses’ attitudes and perceptions in caring for patients with dementia (b), and exploring how nurses deal with challenging behaviour (c). Additionally, we determined background variables associated with caring for people with dementia. BACKGROUND: Due to comorbidities, people with dementia are frequently admitted to acute care hospitals. Here, they are at high risk of complications. Nurses strive for good care but regularly experience insufficient knowledge and skills regarding caring for people with dementia. DESIGN: A cross‐sectional survey study design. METHODS: Data were collected in seven Dutch acute hospitals and through social media. In total, 229 hospital nurses completed the questionnaire. We used the Geriatric In‐Hospital Nursing Care Questionnaire and two subscales of Hynninen on managing challenging behaviour. This report followed the STROBE checklist. RESULTS: Nurses express that they often apply general preventive interventions not explicitly related to dementia care. In general, nurses have mixed feelings about the nursing care provided in their department. For challenging behaviour, a variety of approaches, including restrictive measures and medication, is applied. The nurses’ attitudes and perceptions are influenced by the type of hospital where the nurses work, the level of education, the number of hours nurses work, and if the nurses completed a course on dementia in the last year. CONCLUSIONS: Despite a positive attitude, nurses do not have the specific knowledge and skills needed to provide proper care. Nurses who recently completed a course on dementia had more positive attitudes and perceptions towards caring for patients with dementia. RELEVANCE TO CLINICAL PRACTICE: The results of this research can be used to improve the quality of nursing care for patients with dementia in acute hospitals

Experiences of informal caregivers of people with dementia with nursing care in acute hospitals:A descriptive mixed-methods study

Aims To explore the experiences of informal caregivers of people with dementia with the hospitalization of their relative concerning patient care, interactions with nurses, caregivers' situation and the acute hospital environment. Design Mixed-methods design. Methods The data were collected using an online questionnaire among a panel of caregivers (n = 129), together with a focus group and individual interviews from February to November 2019. The data were triangulated and analysed using a conceptual framework. Results Almost half of the respondents were satisfied with the extent to which nurses considered the patient's dementia. Activities to prevent challenging behaviours and provide person-centred care were rarely seen by the caregivers. Caregivers experienced strain, intensified by a perceived lack of adequate communication and did not feel like partners in care; they also expressed concern about environmental safety. A key suggestion of caregivers was to create a special department for people with dementia, with specialized nurses. Conclusion Positive experiences of caregivers are reported in relation to how nurses take dementia into account, involvement in care and shared decision making. Adverse experiences are described in relation to disease-oriented care, ineffective communication and an unfamiliar environment. Caregivers expressed increased involvement when included in decisions and care when care was performed as described by the triangle of care model. Caregivers reported better care when a person-centred approach was observed. Outcomes can be used in training to help nurses reflect and look for improvements. Impact This study confirms that caregivers perceive that when they are more involved in care, this can contribute to improving the care of patients with dementia. The study is relevant for nurses to reflect on their own experiences and become aware of patients' caregivers' perspectives. It also provides insights to improve nurses' training and for organizations to make the care and environment more dementia-friendly

К проблеме методологического статуса персонализированной медицины как практикоориентарованной учебной дисциплины

МЕДИЦИНСКИЕ УЧЕБНЫЕ ЗАВЕДЕНИЯОБРАЗОВАНИЕ МЕДИЦИНСКОЕСТУДЕНТЫУЧЕБНЫЕ ДИСЦИПЛИНЫПЕРСОНАЛИЗИРОВАННАЯ МЕДИЦИНАПРАКТИКО-ОРИЕНТИРОВАННАЯ ОБРАЗОВАТЕЛЬНАЯ СРЕДАПРАКТИКО-ОРИЕНТИРОВАННОЕ ОБУЧЕНИЕМЕТОДОЛОГИЧЕСКИЕ ПОДХОД

Involvement, topics, and roles of nurses in shared decision-making with patients with dementia in acute hospitals:An integrative review

Aim: To describe nurses' roles, involvement, and topics in shared decision-making with older patients with dementia in acute hospitals. Design: An integrative review. Methods: A systematic search was performed until April 2022 in PubMed, PsychInfo, CINAHL, and Cochrane, followed by a manual search on the reference lists of relevant systematic reviews. Studies were independently screened, appraised using the Joanna Briggs Institute (JBI) methodology, and extracted by two reviewers. Results: Nine studies were included. Nurses were involved as treatment team members, intermediates, or patient supporters. Nurses' roles were most explicit in the preparatory phase of shared decision-making. The step of ‘developing tailor-made options’ was limitedly identified. ‘Deliberating and trying options to reach a decision’ were described from an outsider's perspective in which nurses attempted to influence the decision. In conclusion, nurses primarily have a role in decision-making by supplementing patient information. Patient and Public Contribution No Patient or Public Contribution.</p

Involvement, topics, and roles of nurses in shared decision-making with patients with dementia in acute hospitals:An integrative review

Aim: To describe nurses' roles, involvement, and topics in shared decision-making with older patients with dementia in acute hospitals. Design: An integrative review. Methods: A systematic search was performed until April 2022 in PubMed, PsychInfo, CINAHL, and Cochrane, followed by a manual search on the reference lists of relevant systematic reviews. Studies were independently screened, appraised using the Joanna Briggs Institute (JBI) methodology, and extracted by two reviewers. Results: Nine studies were included. Nurses were involved as treatment team members, intermediates, or patient supporters. Nurses' roles were most explicit in the preparatory phase of shared decision-making. The step of ‘developing tailor-made options’ was limitedly identified. ‘Deliberating and trying options to reach a decision’ were described from an outsider's perspective in which nurses attempted to influence the decision. In conclusion, nurses primarily have a role in decision-making by supplementing patient information. Patient and Public Contribution No Patient or Public Contribution.</p

Involvement, topics, and roles of nurses in shared decision-making with patients with dementia in acute hospitals:An integrative review

Aim: To describe nurses' roles, involvement, and topics in shared decision-making with older patients with dementia in acute hospitals. Design: An integrative review. Methods: A systematic search was performed until April 2022 in PubMed, PsychInfo, CINAHL, and Cochrane, followed by a manual search on the reference lists of relevant systematic reviews. Studies were independently screened, appraised using the Joanna Briggs Institute (JBI) methodology, and extracted by two reviewers. Results: Nine studies were included. Nurses were involved as treatment team members, intermediates, or patient supporters. Nurses' roles were most explicit in the preparatory phase of shared decision-making. The step of ‘developing tailor-made options’ was limitedly identified. ‘Deliberating and trying options to reach a decision’ were described from an outsider's perspective in which nurses attempted to influence the decision. In conclusion, nurses primarily have a role in decision-making by supplementing patient information. Patient and Public Contribution No Patient or Public Contribution.</p

Involvement, topics, and roles of nurses in shared decision-making with patients with dementia in acute hospitals:An integrative review

Aim: To describe nurses' roles, involvement, and topics in shared decision-making with older patients with dementia in acute hospitals. Design: An integrative review. Methods: A systematic search was performed until April 2022 in PubMed, PsychInfo, CINAHL, and Cochrane, followed by a manual search on the reference lists of relevant systematic reviews. Studies were independently screened, appraised using the Joanna Briggs Institute (JBI) methodology, and extracted by two reviewers. Results: Nine studies were included. Nurses were involved as treatment team members, intermediates, or patient supporters. Nurses' roles were most explicit in the preparatory phase of shared decision-making. The step of ‘developing tailor-made options’ was limitedly identified. ‘Deliberating and trying options to reach a decision’ were described from an outsider's perspective in which nurses attempted to influence the decision. In conclusion, nurses primarily have a role in decision-making by supplementing patient information. Patient and Public Contribution No Patient or Public Contribution.</p