1,856 research outputs found
Repurposing bromocriptine for Aβ metabolism in Alzheimer’s disease (REBRAnD) study : randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer’s disease with presenilin 1 (PSEN1) mutations
Introduction
Alzheimer’s disease (AD) is one of the most common causes of dementia. Pathogenic variants in the presenilin 1 (PSEN1) gene are the most frequent cause of early-onset AD. Medications for patients with AD bearing PSEN1 mutation (PSEN1-AD) are limited to symptomatic therapies and no established radical treatments are available. Induced pluripotent stem cell (iPSC)-based drug repurposing identified bromocriptine as a therapeutic candidate for PSEN1-AD. In this study, we used an enrichment strategy with iPSCs to select the study population, and we will investigate the safety and efficacy of an orally administered dose of bromocriptine in patients with PSEN1-AD.
Methods and analysis
This is a multicentre, randomised, placebo-controlled trial. AD patients with PSEN1 mutations and a Mini Mental State Examination-Japanese score of ≤25 will be randomly assigned, at a 2:1 ratio, to the trial drug or placebo group (≥4 patients in TW-012R and ≥2 patients in placebo). This clinical trial consists of a screening period, double-blind phase (9 months) and extension phase (3 months). The double-blind phase for evaluating the efficacy and safety is composed of the low-dose maintenance period (10 mg/day), high-dose maintenance period (22.5 mg/day) and tapering period of the trial drug. Additionally, there is an open-labelled active drug extension period for evaluating long-term safety. Primary outcomes are safety and efficacy in cognitive and psychological function. Also, exploratory investigations for the efficacy of bromocriptine by neurological scores and biomarkers will be conducted.
Ethics and dissemination
The proposed trial is conducted according to the Declaration of Helsinki, and was approved by the Institutional Review Board (K070). The study results are expected to be disseminated at international or national conferences and published in international journals following the peer-review process
Conception d'un clavier musical pour entraîner les fonctions motrices et cognitives dans la maladie d'Alzheimer
La maladie d’Alzheimer (MA) est la cause la plus fréquente de démence chez les personnes âgées. Un traitement n’a pas encore été trouvé, mais des études montrent que la combinaison de thérapies pharmacologiques et non pharmacologiques (TNP) peut ralentir la progression des symptômes de la maladie. Parmi les TNP, la thérapie musicale active ou musicothérapie active (TMA) a été largement utilisée. Cependant, cette approche requiert une supervision constante pour que la thérapie soit exécutée correctement. L’utilisation de technologies adaptées aux besoins des personnes avec MA pourrait alors leur permettre de participer de manière autonome aux sessions de TMA. Ce mémoire de maîtrise s’organise autour de deux articles scientifiques. Le premier est une recension des écrits au sujet de la TMA utilisée en MA. Le deuxième article présente la démarche de co-conception d’un prototype du dispositif de clavier musical surdimensionné capable de guider les utilisateurs atteints de MA (stade léger) à travers des sessions de TMA qui comprennent des activités musicales,cognitives et motrices. Des études complémentaires devront évaluer les effets de l’utilisation de ce dispositif musical sur les différents symptômes de la MA. Cependant, le matériau présenté dans le premier article de la thèse (recension des écrits) et les données en lien avec le deuxième article (co-conception), tels que les témoignages des participants au stage léger de la MA et les prototypes créés, indiquent que l’utilisation de ce clavier peut potentiellement atténuer les symptômes associés à la MA et ainsi améliorer la qualité de la vie de cette population.Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. A cure has not yet been found, but studies show that the combination of pharmacological and non-pharmacological therapies (NPT) can slow down the progression of the symptoms of the disease. Among the NPT, active music therapy (AMT) has been widely used to help relieve the symptoms of dementia. However,most AMT require constant supervision or guidance so that the person with AD can participate in the therapy session and perform it correctly. The use of technologies specifically designed to meet the needs of this population could allow them to autonomously participate in AMT sessions.This master’s thesis is organized into two articles, the first is a literature review regarding the application of AMT in AD. The second article presents the co-design process of an oversized musical keyboard that can guide users with mild AD through AMT sessions that integrate musical, cognitive and motor tasks. Further studies should evaluate the effects of using this device on different symptoms of Alzheimer’s disease. However, the results presented in the first article of the thesis and the observations from the interactions between the participants (with mild AD) and the prototypes provided during the co-design process indicate that the use of this keyboard has the potential to alleviate symptoms related to AD and, thus, improve the quality of life
Recommendations for ICT use in Alzheimer's Disease assessment: Monaco CTAD expert meeting
International audienceAlzheimer disease (AD) and other related dementia represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments for assessing disease severity and disease progression to optimize patient's care and support to care provide rs, and also provide better tools for clinical research. In this area, Information and Communication Technologies (ICT) are of particular interest. Such techniques enable accurate and standardized assessments of patients' performance and actions in real time and real life situations. The aim of this article is to provide basic recommendation concerning the development and the use of ICT for Alzheimer's disease and related disorders. During he ICT and Mental Health workshop (CTAD meeting held in Monaco on the 30th October 2012) an expert panel was set up to prepare the first recommendations for the use of ICT in dementia research. The expert panel included geriatrician, epidemiologist, neurologist, psychiatrist, psychologist, ICT engineers, representatives from the industry and patient association. The recommendations are divided into three sections corresponding to 1/ the clinical targets of interest for the use of ICT, 2/ the cond itions, the type of sensors and the outputs (scores) that could be used and obtained, 3/ finally the last section concerns specifically the use of ICT within clinical trials
Safety of Antipsychotic Medication in Individuals Diagnosed with Autism Spectrum Disorder (ASD)
Background: Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition which presents in childhood. In the UK, risperidone is the only antipsychotic drug approved for the management of behavioural disturbance in children and adolescents with ASD. Aim: To explore the safety of antipsychotic medication use in people with ASD. Method: Four observational studies using a UK primary care database as a data source. The first study was a descriptive study to provide up-to-date information on the prevalence of ASD and psychotropic medication prescribing. Next, two analytical studies, of different designs, to investigate the risk of incident seizure associated with antipsychotic use, were conducted. A cohort study comparing the risk of incident seizure in people using antipsychotics with the users of other psychotropics; followed by a selfcontrolled case series analysis on the risk of incident seizure associated with antipsychotic use. Lastly, a cohort study to investigate the relationship between the risk of cardiac events and antipsychotic exposure, compared to other psychotropics, was conducted. Results: There has been a noticeable increase (3.3-fold) in the prevalence of ASD over the period from 2009 to 2016. Over this period, 12.4% of the treated ASD patients had been prescribed antipsychotics; 50.7% of antipsychotic prescriptions was for risperidone and 49.3% was for other antipsychotics. The hazard ratios of the risk of incident seizure and cardiac events associated with antipsychotic use were 1.28 (95% CI: 0.74-2.19) and 1.27 (95% CI: 0.62-2.62), respectively. During the first month of other psychotropic medication treatment, the incidence rate ratio of seizure was 1.57, 95% CI:1.03-2.38. Conclusion: This research found no evidence of an increased risk of incident seizure or cardiac outcomes associated with antipsychotic use compared to other psychotropics ASD patients. A short term increase in the risk of incident seizure was noted with the use of psychotropics other than antipsychotics
Neuropsychological assessment for first-episode psychosis patients in low resource settings
Introduction: Cognitive impairment is the most significant predictor of long-term outcomes in psychotic disorders, and neuropsychological assessment is therefore recommended in first-episode psychosis patients. However, the literature on neuropsychological assessment for first-episode psychosis patients in low resource settings is limited, the clinical utility of such assessments are unclear, and lengthy assessments may not be practicable in these contexts. This thesis therefore investigated 1) which brief neuropsychological assessment measures researched in patients with psychotic disorders from low and middle-income countries are appropriate for cognitive screening, 2) the differences in prevalence and profile of cognitive impairment between first-episode psychosis patients and healthy peers in one low resource setting, 3) the association of clinical variables with impairment in different cognitive domains in first-episode psychosis patients from one low resource setting, and 4) the validity of the NeuroScreen (a collection of brief neuropsychological test delivered via smartphone) for neuropsychological assessment in first-episode psychosis patients in this setting (as determined by comparison with a gold standard evaluation). Methods: First, a systematic review of articles in which brief neuropsychological assessments were researched in patients with psychotic disorders from low and middle-income countries was performed. The 2014 Working Group on Screening and Assessment (WGSA) guidelines were used as a benchmark of the appropriateness for cognitive screening for the neuropsychological assessment measures employed. Second, first-episode psychosis patients and matched healthy peers were recruited into an observational study at the National mental referral hospital in Uganda. Clinical variables were collated (including sociodemographic characteristics, dietary history, previous childhood trauma and illness severity), and after the resolution of psychotic symptoms, a neuropsychological assessment was performed using the gold standard MATRICS consensus cognitive battery. Student t-tests and chi-square tests were used to determine differences in the prevalence and profile of cognitive impairment in patients with psychosis and healthy peers. Multiple linear regression analyses were used to determined associations between clinical variables and cognitive domains while controlling for potential confounders. Finally, Pearson's rank correlation coefficients and receiver operating curves were computed to examine the validity of the NeuroScreen against the MATRICS consensus cognitive battery. Results: In the 29 articles reviewed, none of the neuropsychological measures researched in patients with psychotic disorders of low and middle-income countries was appropriate for cognitive screening according to the Working Group on Screening and Assessment (WGSA) guidelines. Neuropsychological assessment with the MATRICS consensus cognitive battery found the burden of cognitive impairment in first-episode psychosis patients six times that of healthy peers. The largest cognitive impairment burden was in the visual learning and memory domain. Increased age was associated with impairment in the domains of the speed of processing (p= 0.001). . Cassava rich diets had a negative association with cognitive impairment in the visual learning and memory domain (p=0.04). There were no significant associations between sex, history of childhood trauma or illness severity with any of the seven cognitive domains. A composite score from five cognitive domains of the NeuroScreen had a moderate accuracy of 0.79 compared to the MATRICS consensus cognitive battery. Conclusion: There is need for further research on appropriate measures for neuropsychological assessment in low resource settings. As demonstrated here, the use of such assessments may reveal modifiable risk factors for such impairment; appropriate nutrition may be a particularly important intervention for individuals with psychotic disorders in poorly resourced settings. The NeuroScreen may be useful for neuropsychological assessment of patients with psychotic disorders in low resource settings but needs modification to improve its accuracy
The nurse of the Mediterranean
During the First World War Malta did not take an active part in the fighting. Britain was joined in an ‘entente’ a friendship agreement with France since 1904 and later with Russia in 1907. On the other hand Germany was allied to the Austrian- Hungerian Empire, hence when the Great War started in July 1914 there were France, Britain and Russia on one side and Germany and Austria-Hungary on the other. The British fleet “ruled the waves”, hence with France and Britain as allies, to be joined later by Italy, the Mediterranean was more or less an allied lake, with Malta in the centre.peer-reviewe
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