Project description:The clinical adoption of psychiatric pharmacogenomic testing has taken place rapidly over the past 7 years. Initially, drug-metabolizing enzyme genes, such as the cytochrome P450 2D6 gene (CYP2D6), were identified. Genotyping the highly variable cytochrome P450 2D6 gene now provides clinicians with the opportunity to identify both poor metabolizers and ultrarapid metabolizers of 2D6 substrate medications. Subsequently, genes influencing the pharmacodynamic response of medications have been made available for clinical practice. Among the earliest "target genes" was the serotonin transporter gene (SLC6A4) which has variants that have been shown to influence the clinical response of patients of European ancestry when they are treated with selective serotonin reuptake inhibitors. Genotyping of some of the serotonin receptor genes is also available to guide clinical practice. The quantification of the clinical utility of pharmacogenomic testing is evolving, and ethical considerations for testing have been established. Given the increasingly clear cost-effectiveness of genotyping, it has recently been predicted that pharmacogenomic testing will routinely be ordered to guide the selection and dosing of psychotropic medications.
Project description:BackgroundA significant number of people with autism require in-patient psychiatric care. Although the requirement to adequately meet the needs of people with autism in these settings is enshrined in UK law and supported by national guidelines, little information is available on current practice.AimsTo describe characteristics of UK in-patient psychiatric settings admitting people with autism. Also to examine psychiatric units for their suitability, and the resultant impact on admission length and restrictive interventions.MethodMultiple-choice questions about in-patient settings and their ability to meet the needs of people with autism and the impact on their outcomes were developed as a cross-sectional study co-designed with a national autism charity. The survey was distributed nationally, using an exponential and non-discriminatory snowballing technique, to in-patient unit clinicians to provide a current practice snapshot.ResultsEighty responses were analysed after excluding duplications, from across the UK. Significant variation between units across all enquired parameters exist. Lack of autism-related training and skills across staff groups was identified, this becoming disproportionate when comparing intellectual disability units with general mental health units particularly regarding psychiatrists working in these units (psychiatrists: 94% specialist skills in intellectual disability units versus 6% specialist skills in general mental health units). In total, 28% of survey respondents felt people with autism are more likely to be subject to seclusion and 40% believed in-patients with autism are likely to end in segregation.ConclusionsThere is no systematic approach to supporting people with autism who are admitted to in-patient psychiatric units. Significant concerns are highlighted of lack of professional training and skill sets resulting in variable clinical practice and care delivery underpinned by policy deficiency. This could account for the reported in-patient outcomes of longer stay and segregation experienced by people with autism.
Project description:Psychiatric disorders are highly prevalent brain pathologies that represent an urgent, unmet biomedical problem. Since reliable clinical diagnoses are essential for the treatment of psychiatric disorders, their animal models with robust, relevant behavioral and physiological endpoints become necessary. Zebrafish (Danio rerio) display well-defined, complex behaviors in major neurobehavioral domains which are evolutionarily conserved and strikingly parallel to those seen in rodents and humans. Although zebrafish are increasingly often used to model psychiatric disorders, there are also multiple challenges with such models as well. The field may therefore benefit from a balanced, disease-oriented discussion that considers the clinical prevalence, the pathological complexity, and societal importance of the disorders in question, and the extent of its detalization in zebrafish central nervous system (CNS) studies. Here, we critically discuss the use of zebrafish for modeling human psychiatric disorders in general, and highlight the topics for further in-depth consideration, in order to foster and (re)focus translational biological neuroscience research utilizing zebrafish. Recent developments in molecular biology research utilizing this model species have also been summarized here, collectively calling for a wider use of zebrafish in translational CNS disease modeling.
Project description:Pharmacogenomics (i.e., the application of genetic information in predicting an individual's response to drug therapy) plays an increasingly important role in drug development and decision-making regarding precision medicine. This has been shown to reduce the risk of adverse events and improve patient health-care outcomes through targeted therapies and dosing. As the field of pharmacogenomics rapidly evolves, the role of pharmacists in the education, implementation, and research applications of pharmacogenomics is becoming increasingly recognized. This paper aims to provide an overview and current perspectives of pharmacogenomics in contemporary clinical pharmacy practice and to discuss the future directions on advancing pharmacogenomics education, application, and research in pharmacy practice.
Project description:BackgroundIn Indonesia, the burden of severe hyperbilirubinemia is higher compared to other countries. Whether this is related to ineffective phototherapy (PT) is unknown. The aim of this study is to investigate the performance of phototherapy devices in hospitals on Java, Indonesia.MethodsIn 17 hospitals we measured 77 combinations of 20 different phototherapy devices, with and without curtains drawn around the incubator/crib. With a model to mimic the silhouette of an infant, we measured the irradiance levels with an Ohmeda BiliBlanket Meter II, recorded the distance between device and model, and compared these to manufacturers' specifications.ResultsIn nine hospitals the irradiance levels were less than required for standard PT: < 10 μW/cm2/nm and in eight hospitals irradiance failed to reach the levels for intensive phototherapy: 30 μW/cm2/nm. Three hospitals provided very high irradiance levels: > 50 μW/cm2/nm. Half of the distances between device and model were greater than recommended. Distance was inversely correlated with irradiance levels (R2 = 0.1838; P < 0.05). The effect of curtains on irradiance levels was highly variable, ranging from - 6.15 to + 15.4 μW/cm2/nm, with a mean difference (SD) of 1.82 (3.81) μW/cm2/nm (P = 0.486).ConclusionsIn half of the hospitals that we studied on Java the levels of irradiance are too low and, in some cases, too high. Given the risks of insufficient phototherapy or adverse effects, we recommend that manufacturers provide radiometers so hospitals can optimize the performance of their phototherapy devices.
Project description:Application of 200 µA of direct current to bacterial biofilms leads to cellular death. We hypothesize that bacterial death is caused, in part, by the generation of reactive oxygen species. We used microarray analysis to determine the effects at a cellular level following 60 minutes of exposure of bacterial biofilms to 200 µA direct current.
Project description:The use of 3D printing in orthopedic trauma is supported by clinical evidence. Existing computed tomography (CT) data are exploited for better stereotactic identification of morphological features of the fracture and enhanced surgical planning. Due to complex logistic, technical and resource constraints, deployment of 3D printing is not straightforward from the hospital management perspective. As a result not all trauma surgeons are able to confidently integrate 3D printing into the daily practice. We carried out an expert panel survey on six trauma units which utilized 3D printing routinely. The most frequent indications are acetabular and articular fractures and malalignments. Infrastructure and manpower structure varied between units. The installation of industrial grade machines and dedicated software as well as the use of trained personnel can enhance the capacity and reliability of fracture treatment. Setting up interdisciplinary jointly used 3d printing departments with sound financial and management structures may improve sustainability. The sometimes substantial logistic and technical barriers which impede the rapid delivery of 3D printed models are discussed.
Project description:Cumulating evidence for the involvement of mitochondrial dysfunction in psychiatric disorders leaves little to no doubt regarding the involvement of this pathology in mood disorders. However, mitochondrial abnormalities are also observed in a wide range of disorders spanning from cancer and diabetes to various neurodegenerative and neurodevelopmental disorders such as Parkinson's, Alzheimer's, Huntington's, autism, and amyotrophic lateral sclerosis. The apparent lack of specificity questions the role of mitochondrial dysfunction in psychiatric disorders, in general, and in mood disorders, in particular. Is mitochondrial dysfunction a general phenomenon, simplistically rendering brain cells to be more vulnerable to a variety of disease-specific perturbations? Or is it an epiphenomenon induced by various disease-specific factors? Or possibly, the severity and the anatomical region of the dysfunction are the ones responsible for the distinct features of the disorders. Whichever of the aforementioned ones, if any, is correct, "mitochondrial dysfunction" became more of a cliché than a therapeutic target. In this review, we summarize current studies supporting the involvement of mitochondrial dysfunction in different psychiatric disorders. We address the question of specificity and causality of the different findings and provide an alternative explanation for some of the aforementioned questions.
Project description:Effective pharmacologic treatments for psychiatric disorders are available, but their effect is limited due to patients' genetic heterogeneity and low compliance-related to frequent adverse events. Only one third of patients respond to treatment and experience remission. Pharmacogenetics is a relatively young field which focusses on genetic analyses in the context of the metabolism and outcome of drug treatment. These genetic factors can, among other things, lead to differences in the activity of enzymes that metabolize drugs. Recently, a clinical guideline was authorized by the Dutch Clinical Psychiatric Association (NVvP) on the clinical use of pharmacogenetics in psychiatry. The main goal was to provide guidance, based on current evidence, on how to best use genotyping in clinical psychiatric practice. A systematic literature search was performed, and available publications were assessed using the GRADE methodology. General recommendations for psychiatric clinical practice were provided, and specific recommendations per medication were made available. This clinical guideline for caregivers prescribing psychotropic drugs is the product of a broad collaboration of professionals from different disciplines, making use of the information available at the Dutch Pharmacogenetics Working Group (DPWG) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) so far. We summarize the relevant literature and all recommendations in this article. General recommendations are provided and also detailed recommendations per medication. In summary we advise to consider genotyping, when there are side effects or inefficacy for CYP2C19 and CYP2D6. When genotype information is available use this to select the right drug in the right dose for the right patient.
Project description:Human milk (HM) is considered the gold standard for infant nutrition. HM contains macro- and micronutrients, as well as a range of bioactive compounds (hormones, growth factors, cell debris, etc.). The analysis of the complex and dynamic composition of HM has been a permanent challenge for researchers. The use of novel, cutting-edge techniques involving different metabolomics platforms has permitted to expand knowledge on the variable composition of HM. This review aims to present the state-of-the-art in untargeted metabolomic studies of HM, with emphasis on sampling, extraction and analysis steps. Workflows available from the literature have been critically revised and compared, including a comprehensive assessment of the achievable metabolome coverage. Based on the scientific evidence available, recommendations for future untargeted HM metabolomics studies are included.