Exploring the relationship between age and health conditions using electronic health records: from single diseases to multimorbidities

Background Two enormous challenges facing healthcare systems are ageing and multimorbidity. Clinicians, policymakers, healthcare providers and researchers need to know “who gets which diseases when” in order to effectively prevent, detect and manage multiple conditions. Identification of ageing-related diseases (ARDs) is a starting point for research into common biological pathways in ageing. Examining multimorbidity clusters can facilitate a shift from the single-disease paradigm that pervades medical research and practice to models which reflect the reality of the patient population. Aim To examine how age influences an individual’s likelihood of developing single and multiple health conditions over the lifecourse. Methods and Outputs I used primary care and hospital admission electronic health records (EHRs) of 3,872,451 individuals from the Clinical Practice Research Datalink (CPRD) linked to the Hospital Episode Statistics admitted patient care (HES-APC) dataset in England from 1 April 2010 to 31 March 2015. In collaboration with Professor Aroon Hingorani, Dr Osman Bhatti, Dr Shanaz Husain, Dr Shailen Sutaria, Professor Dorothea Nitsch, Mrs Melanie Hingorani, Dr Constantinos Parisinos, Dr Tom Lumbers and Dr Reecha Sofat, I derived the case definitions for 308 clinically important health conditions, by harmonising Read, ICD-10 and OPCS-4 codes across primary and secondary care records in England. I calculated the age-specific incidence rate, period prevalence and median age at first recorded diagnosis for these conditions and described the 50 most common diseases in each decade of life. I developed a protocol for identifying ARDs using machine-learning and actuarial techniques. Finally, I identified highly correlated multimorbidity clusters and created a tool to visualise comorbidity clusters using a network approach. Conclusions I have developed case definitions (with a panel of clinicians) and calculated disease frequency estimates for 308 clinically important health conditions in the NHS in England. I have described patterns of ageing and multimorbidity using these case definitions, and produced an online app for interrogating comorbidities for an index condition. This work facilitates future research into ageing pathways and multimorbidity

Gluten-Related Disorders: Time to Move from Gut to Brain

The extraintestinal manifestations of coeliac disease (CD) are now well recognised. We have previously edited a special issue for Nutrients covering all aspects of the extraintestinal manifestations in the context of CD. In this issue we wish to concentrate just on the neurological manifestations. The identification of TG6 autoantibodies in patients with neurological manifestations and its use in the diagnosis of such patients seems to be a good opportunity to focus on the neurological aspect of CD. In addition it is now clear that such manifestations can occur even in the absence of enteropathy but in the presence of antigliadin antibodies and/or TG6 antibodies. Given that such antigliadin antibodies can be found in up to 10% of the “healthy” population we anticipate that the neurological manifestations are likely to be very common and thus merit early recognition and treatment

Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior

There is a growing recognition of the importance of the commensal intestinal microbiota in the development and later function of the central nervous system. Research using germ-free mice (mice raised without any exposure to microorganisms) has provided some of the most persuasive evidence for a role of these bacteria in gut-brain signalling. Key findings show that the microbiota is necessary for normal stress responsivity, anxiety-like behaviors, sociability, and cognition. Furthermore, the microbiota maintains central nervous system homeostasis by regulating immune function and blood brain barrier integrity. Studies have also found that the gut microbiota influences neurotransmitter, synaptic, and neurotrophic signalling systems and neurogenesis. The principle advantage of the germ-free mouse model is in proof-of-principle studies and that a complete microbiota or defined consortiums of bacteria can be introduced at various developmental time points. However, a germ-free upbringing can induce permanent neurodevelopmental deficits that may deem the model unsuitable for specific scientific queries that do not involve early-life microbial deficiency. As such, alternatives and complementary strategies to the germ-free model are warranted and include antibiotic treatment to create microbiota-deficient animals at distinct time points across the lifespan. Increasing our understanding of the impact of the gut microbiota on brain and behavior has the potential to inform novel management strategies for stress-related gastrointestinal and neuropsychiatric disorders

A novel gluten knowledge base of potential biomedical and health-related interactions extracted from the literature: using machine learning and graph analysis methodologies to reconstruct the bibliome

Background In return for their nutritional properties and broad availability, cereal crops have been associated with different alimentary disorders and symptoms, with the majority of the responsibility being attributed to gluten. Therefore, the research of gluten-related literature data continues to be produced at ever-growing rates, driven in part by the recent exploratory studies that link gluten to non-traditional diseases and the popularity of gluten-free diets, making it increasingly difficult to access and analyse practical and structured information. In this sense, the accelerated discovery of novel advances in diagnosis and treatment, as well as exploratory studies, produce a favourable scenario for disinformation and misinformation. Objectives Aligned with, the European Union strategy “Delivering on EU Food Safety and Nutrition in 2050″ which emphasizes the inextricable links between imbalanced diets, the increased exposure to unreliable sources of information and misleading information, and the increased dependency on reliable sources of information; this paper presents GlutKNOIS, a public and interactive literature-based database that reconstructs and represents the experimental biomedical knowledge extracted from the gluten-related literature. The developed platform includes different external database knowledge, bibliometrics statistics and social media discussion to propose a novel and enhanced way to search, visualise and analyse potential biomedical and health-related interactions in relation to the gluten domain. Methods For this purpose, the presented study applies a semi-supervised curation workflow that combines natural language processing techniques, machine learning algorithms, ontology-based normalization and integration approaches, named entity recognition methods, and graph knowledge reconstruction methodologies to process, classify, represent and analyse the experimental findings contained in the literature, which is also complemented by data from the social discussion. Results and conclusions In this sense, 5814 documents were manually annotated and 7424 were fully automatically processed to reconstruct the first online gluten-related knowledge database of evidenced health-related interactions that produce health or metabolic changes based on the literature. In addition, the automatic processing of the literature combined with the knowledge representation methodologies proposed has the potential to assist in the revision and analysis of years of gluten research. The reconstructed knowledge base is public and accessible at https://sing-group.org/glutknois/Fundação para a Ciência e a Tecnologia | Ref. UIDB/50006/2020Xunta de Galicia | Ref. ED481B-2019-032Xunta de Galicia | Ref. ED431G2019/06Xunta de Galicia | Ref. ED431C 2022/03Universidade de Vigo/CISU

Insomnia in obsessive-compulsive disorder and body dysmorphic disorder

El insomnio es un problema de salud pública que tiene importantes consecuencias negativas para los individuos que lo padecen. Un número creciente de estudios científicos propone una relación bidireccional entre el insomnio y las enfermedades psiquiátricas, sin embargo, la evidencia científica disponible respecto a la prevalencia de insomnio en el trastorno obsesivo-compulsivo (TOC) y en el trastorno dismórfico corporal (TDC), tanto en pacientes adultos como en población infanto-juvenil, era escasa hasta la elaboración de esta tesis doctoral. Mediante la elaboración de 3 artículos científicos, publicados en revistas científicas de ámbito internacional, se estudió la asociación entre el insomnio y las patologías psiquiátricas mencionadas anteriormente, obteniéndose las siguientes conclusiones: o La prevalencia de insomnio en el TOC a nivel poblacional es de aproximadamente 42% y las personas con TOC presentan 7 veces más probabilidades de sufrir insomnio que aquellas personas sin TOC en la población general. o Los factores familiares compartidos con los hermanos y la presencia de comorbilidad psiquiátrica no explican por completo la asociación entre insomnio y TOC, aunque la exclusión de individuos con una depresión o un trastorno de ansiedad comórbidos atenuó significativamente las probabilidades de padecer insomnio. o La prevalencia de insomnio en niños y adolescentes con TOC atendidos en una clínica especializada, coincide con la prevalencia de insomnio de los pacientes con TOC vistos en servicios especializados en la población general (42%). o El insomnio en niños y adolescentes con TOC se asocia con una mayor gravedad de la sintomatología obsesiva-compulsiva y depresiva, así como con un peor nivel general de funcionamiento. o En nuestra muestra de pacientes pediátricos con TOC atendidos en una clínica especializada, el insomnio pareció no interferir en la respuesta al tratamiento multimodal para el TOC. o El insomnio es muy prevalente en niños y adolescentes con TDC que acuden a una clínica especializada en el tratamiento de dicho trastorno (48,5%)

Identification of Biomarker Systems of Autism Spectrum Disorder and Uterine Cancer

Complex diseases and disorders pose a challenge to scientists due to their variable and often inconsistent genetic and environmental underpinnings across affected individuals. Because of this variability, large condition-specific datasets and corresponding analytical tools and approaches are being curated as resources to investigate potential genetic trends in complex diseases and disorders. In this Dissertation, I used DNA- and RNA-based resources to discover polygenic biosignatures associated with Autism Spectrum Disorder (ASD) or uterine cancer. To explore the intersection of small-effect common DNA variants and regulation in ASD, I discovered and analyzed trends in allelic associations at eQTLs within ASD-affected individuals. Association of eQTLs underlying any phenotype brings the genetic variation closer to biochemical mechanism leading to phenotypic expression. Uterine cancer was additionally investigated using gene expression profiles from normal and cancerous uterine tissue samples, from which gene co-expression networks and corresponding gene regulatory networks were built and further studied. The biomarker discoveries discussed here reflect the importance of dry lab resources and the potential they hold for future discovery

Diet and Microbiome in Health and Aging

Diet plays a fundamental role in shaping the composition and metabolic activity of the gut microbiota and, thus, it could determine the interrelationship between the gut microbiome and the host. The colon is the part of the human body that is most densely populated, containing bacteria, archaea, viruses, and some unicellular eukaryotes that have co-evolved with humans in a commensal way. The gut microbiota plays a crucial role in the maintenance of normal host physiology. The rapid development of next-generation sequencing (NGS) methods for DNA sequencing in the last decade has facilitated in-depth study of gut microbiome composition and function. These methods have contributed to providing evidence regarding the relevance of the intestinal microbiota for host health as well as the basis for putative dietary interventions aimed at counteracting microbiota dysbiosis. Understanding the complex and dynamic interaction between dietary exposures and gut microbiota can help to elucidate their potential role in different pathologies and to guide future strategies for the prevention and treatment of diseases. Age-related changes in the gut microbiome are also associated with physiological changes in the gastrointestinal tract as well as in dietary patterns, with a concomitant decline in the normal function of the immune system that may contribute to increased risk of infection and frailty. More studies are needed to better understand how the microbiota shifts with different environmental factors and how they are associated with dietary changes

The Health of Children and Young People with Chronic Conditions and Disabilities in New Zealand 2016

This report aims to assist district health boards to plan to meet current and future demands in order to improve the quality of life for children with disabilities and chronic conditions by providing: 1. Information from a range of routinely collected data on children and young people’s disability and chronic conditions, including prevalence of conditions arising in the perinatal period 2. Information about children’s and young people’s use of secondary health services 3. Evidence for good practice derived from current policies, guidelines and evidence-based interventions for each of the indicators presented The choice of indicators included in this report was informed by an indicator framework developed by the NZ Child and Youth Epidemiology Service and by recent peer-reviewed literature about chronic conditions in children and young people. Chronic conditions and disabilities often affect people for life. Having a good quality of life and flourishing to your best ability is dependent, at least in part, on what happened as you were growing up. Understanding the dimensions of chronic conditions and disabilities among children and young people is essential to planning and developing good quality health services for New Zealand’s children and young people