Day hospital versus admission for acute psychiatric disorders

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Day hospital versus admission for acute psychiatric disorders

BACKGROUND: Inpatient treatment is an expensive way of caring for people with acute psychiatric disorders. It has been proposed that many of those currently treated as inpatients could be cared for in acute psychiatric day hospitals. OBJECTIVES: To assess the effects of day hospital versus inpatient care for people with acute psychiatric disorders. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (January 1966 to December 2000), EMBASE (1980 to December 2000), CINAHL (1982 to December 2000), PsycLIT (1966 to December 2000), and the reference lists of articles. We approached trialists to identify unpublished studies. SELECTION CRITERIA: Randomised controlled trials of day hospital versus inpatient care, for people with acute psychiatric disorders. Studies were ineligible if a majority of participants were under 18 or over 65, or had a primary diagnosis of substance abuse or organic brain disorder. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers and cross-checked. Relative risks and 95% confidence intervals (CI) were calculated for dichotomous data. Weighted or standardised means were calculated for continuous data. Day hospital trials tend to present similar outcomes in slightly different formats, making it difficult to synthesise data. Individual patient data were therefore sought so that outcomes could be reanalysed in a common format. MAIN RESULTS: Nine trials (involving 1568 people) met the inclusion criteria. Individual patient data were obtained for four trials (involving 594 people). Combined data suggested that, at the most pessimistic estimate, day hospital treatment was feasible for 23% (n=2268, CI 21 to 25) of those currently admitted to inpatient care. Individual patient data from three trials showed no difference in number of days in hospital between day hospital patients and controls (n=465, 3 RCTs, WMD -0.38 days/month CI -1.32 to 0.55). However, compared to controls, people randomised to day hospital care spent significantly more days in day hospital care (n=265, 3 RCTs, WMD 2.34 days/month CI 1.97 to 2.70) and significantly fewer days in inpatient care (n=265, 3 RCTs, WMD -2.75 days/month CI -3.63 to -1.87). There was no significant difference in readmission rates between day hospital patients and controls (n=667, 5 RCTs, RR 0.91 CI 0.72 to 1.15). For patients judged suitable for day hospital care, individual patient data from three trials showed a significant time-treatment interaction, indicating a more rapid improvement in mental state (n=407, Chi-squared 9.66, p=0.002), but not social functioning (n=295, Chi-squared 0.006, p=0.941) amongst patients treated in the day hospital. Four of five trials found that day hospital care was cheaper than inpatient care (with cost reductions ranging from 20.9 to 36.9%). REVIEWER'S CONCLUSIONS: Caring for people in acute day hospitals can achieve substantial reductions in the numbers of people needing inpatient care, whilst improving patient outcome

Transcriptomic and Functional Analysis of Neuronal Activity and Disease

Advances in sequencing technologies have sparked the discovery of new genetic etiologies for neurological and neurodevelopmental disorders. As new disease-causing mutations are unveiled, questions into the specific mechanisms of pathogenicity and potential therapeutic approaches arise. To address these questions, in vivo and in vitro models have been generated and analyzed; but how best to utilize these models, and how well they recapitulate the human brain, is still not fully understood. Within the work discussed in this thesis, we address this problem through the transcriptomic and functional interrogation of these models in the context of neurodevelopment and disease. In Chapter 2 of this thesis, we describe the use of single-cell RNA-sequencing to examine the longitudinal transcriptomic profiles of neuronal network establishment and maturation in ex vivo mouse cortex- and hippocampus-derived cultures. Our data highlights unique developmental transcriptomic profiles for individual genes, disease gene subclasses, and biological processes, and discusses cell population-specific divergent transcriptomic profiles between genes associated with neurological diseases, focusing on epilepsy and autism spectrum disorder. We also compared the data from our ex vivo system to transcriptomic data collected from in vivo neonatal and adult mouse brains and human cortical organoids, highlighting the importance of the generation and consideration of system-specific transcriptomic datasets when looking into a gene, disease, or biological process of interest, and serves as a vital resource for researchers. In Chapter 3, we propose a high-throughput drug discovery paradigm utilizing the application of transcriptome reversal for neurodevelopmental disorder-associated genes that affect the transcriptome. This approach describes the idea that if gene dysregulation is causal for the pathogenicity of a disease, then correcting the transcriptional signature should have a therapeutic effect. We demonstrated that small-molecule induced gene expression changes vary between both cell lines and neural cell populations, and highlight both the importance of selecting the appropriate model of disease and creating cell population-specific signatures for compounds and disease. In Chapter 4, we focus on the utilization of multi-electrode arrays for the electrophysiological characterization of primary cortical networks derived from mouse models of epileptic encephalopathy. This technique allows for the analysis of numerous neuronal and network synchronization metrics for spontaneous longitudinal activity and responses to external stimuli in the form of electrical stimulation and compound addition. In particular, mouse models with mutations in the genes Grin2a, Gnb1, and Scn1a were analyzed. We discovered significant hyperexcitability, bursting, and synchrony phenotypes, and discuss how acute and chronic compound addition can be used to interrogate biological pathways and reverse disease activity signatures

Evidence of shared transcriptomic dysregulation of HNRNPU-related disorder between human organoids and embryonic mice

Summary: Generating effective therapies for neurodevelopmental disorders has remained elusive. An emerging drug discovery approach for neurodevelopmental disorders is to characterize transcriptome-wide dysregulation in an appropriate model system and screen therapeutics based on their capacity to restore functionally relevant expression patterns. We characterized transcriptomic dysregulation in a human model of HNRNPU-related disorder to explore the potential of such a paradigm. We identified widespread dysregulation in functionally relevant pathways and then compared dysregulation in a human model to transcriptomic differences in embryonic and perinatal mice to determine whether dysregulation in an in vitro human model is partially replicated in an in vivo model of HNRNPU-related disorder. Strikingly, we find enrichment of co-dysregulation between 45-day-old human organoids and embryonic, but not perinatal, mice from distinct models of HNRNPU-related disorder. Thus, hnRNPU deficient human organoids may only be suitable to model transcriptional dysregulation in certain cell types within a specific developmental time window