788 research outputs found

    Mental illness in chronic kidney disease : prognosis, drug utilization, and treatment outcomes

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    Chronic kidney disease (CKD) is a common yet heterogeneous condition, covering a wide spectrum of disease severity ranging from mildly decreased kidney function to kidney failure. Patients with CKD can often encounter mental health conditions that are related to poor prognosis. Depression is the most studied mental illness, while previous research has primarily focused on patients with kidney failure undergoing dialysis. Antidepressant medications are the main pharmacological approach for treating depression, with selective serotonin reuptake inhibitors (SSRIs) being the most frequently prescribed type. Notably, antidepressants may have different risk-benefit profiles in CKD patients, for whom dose adjustments are recommended. However, the implementation of SSRI dose adjustment in routine care is largely unknown. Despite the widespread use, there remains uncertainty about the efficacy and safety of antidepressants in the CKD population due to limited clinical evidence, whereas a few observational studies have reported several adverse health outcomes associated with antidepressant use in patients with CKD. In addition, little is known about the burden of bipolar disorder and schizophrenia, less common but severe mental illnesses, in patients with CKD. This thesis aims to expand existing knowledge about the prevalence and impact of mental illnesses, as well as the utilization and safety of antidepressants in patients with CKD. Study I evaluated to what extent patients’ kidney function influences SSRI dosing in routine practice. We found that a lower estimated glomerular filtration rate (eGFR) was moderately associated with being prescribed SSRIs with a reduced initial or maintenance dose. Nonetheless, two-fifths of patients with severely decreased eGFR received SSRI prescriptions without proper dose reduction, potentially exposed to a higher risk of adverse drug reactions. Study II examined the association between an incident diagnosis of depression and adverse clinical outcomes in patients with non-dialysis CKD. We found significant associations between incident depression and hospitalization, CKD progression, major adverse cardiovascular events, and all-cause mortality in patients with non-dialysis CKD. The association with CKD progression became more evident one year after the depression diagnosis, while the associations with the other outcomes were more pronounced within the first year after diagnosis. Study III investigated the comparative safety of antidepressant treatment in patients with CKD and incident depression, using the target trial emulation framework. We found that compared with non-initiation, initiation of antidepressants was associated with a higher risk of short-term adverse events such as hip fracture and upper gastrointestinal bleeding, but was not associated with long-term outcomes, including all-cause mortality, major adverse cardiovascular events, CKD progression, and suicidal behavior. Selection of the appropriate type and dosage of antidepressants is crucial to improve treatment safety. Initiating mirtazapine versus SSRIs was associated with a lower risk of upper gastrointestinal bleeding but a higher risk of mortality. Initiating SSRIs with a reduced dose versus a standard dose was associated with lower risks of upper gastrointestinal bleeding and CKD progression but a higher risk of cardiac arrest. Study IV described the prevalence of three severe mental illnesses (i.e., depression, bipolar disorder, and schizophrenia) and examined their impact on clinical outcomes in patients with CKD. In a nationwide cohort of nephrologist-referred CKD patients, we estimated a prevalence of 5.4% for depression, 1.9% for bipolar disorder, and 0.5% for schizophrenia, amounting to an overall prevalence of 7% for any of these disorders, which was 60% higher than the general population. We found that each of the disorders was associated with a higher mortality rate and bipolar disorder was also associated with a faster eGFR decline. Nevertheless, CKD patients with bipolar disorder or schizophrenia exhibited a lower rate of initiating kidney replacement therapy, suggesting potential inequities in access to this life-sustaining treatment. In conclusion, the present thesis highlights the commonness and negative impact of mental illness in patients with CKD and provides real-world evidence on the prescribing and safety of antidepressants in the CKD population

    Implementing precision methods in personalizing psychological therapies: barriers and possible ways forward

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    This is the final version. Available on open access from Elsevier via the DOI in this recordData availability: No data was used for the research described in the article.Highlights: • Personalizing psychological treatments means to customize treatment for individuals to enhance outcomes. • The application of precision methods to clinical psychology has led to data-driven psychological therapies. • Applying data-informed psychological therapies involves clinical, technical, statistical, and contextual aspects

    Talking about personal recovery in bipolar disorder: Integrating health research, natural language processing, and corpus linguistics to analyse peer online support forum posts

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    Background: Personal recovery, ‘living a satisfying, hopeful and contributing lifeeven with the limitations caused by the illness’ (Anthony, 1993) is of particular value in bipolar disorder where symptoms often persist despite treatment. So far, personal recovery has only been studied in researcher-constructed environments (interviews, focus groups). Support forum posts can serve as a complementary naturalistic data source. Objective: The overarching aim of this thesis was to study personal recovery experiences that people living with bipolar disorder have shared in online support forums through integrating health research, NLP, and corpus linguistics in a mixed methods approach within a pragmatic research paradigm, while considering ethical issues and involving people with lived experience. Methods: This mixed-methods study analysed: 1) previous qualitative evidence on personal recovery in bipolar disorder from interviews and focus groups 2) who self-reports a bipolar disorder diagnosis on the online discussion platform Reddit 3) the relationship of mood and posting in mental health-specific Reddit forums (subreddits) 4) discussions of personal recovery in bipolar disorder subreddits. Results: A systematic review of qualitative evidence resulted in the first framework for personal recovery in bipolar disorder, POETIC (Purpose & meaning, Optimism & hope, Empowerment, Tensions, Identity, Connectedness). Mainly young or middle-aged US-based adults self-report a bipolar disorder diagnosis on Reddit. Of these, those experiencing more intense emotions appear to be more likely to post in mental health support subreddits. Their personal recovery-related discussions in bipolar disorder subreddits primarily focussed on three domains: Purpose & meaning (particularly reproductive decisions, work), Connectedness (romantic relationships, social support), Empowerment (self-management, personal responsibility). Support forum data highlighted personal recovery issues that exclusively or more frequently came up online compared to previous evidence from interviews and focus groups. Conclusion: This project is the first to analyse non-reactive data on personal recovery in bipolar disorder. Indicating the key areas that people focus on in personal recovery when posting freely and the language they use provides a helpful starting point for formal and informal carers to understand the concerns of people diagnosed with bipolar disorder and to consider how best to offer support

    The Application of Simulation to Quantifying the Influence of Bias in Perinatal Epidemiology

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    Perinatal aetiological associations derived from observational data are susceptible to various types of bias. This thesis demonstrated the application of simulation methodologies to quantify the influence of bias in perinatal epidemiology through a series of simulation studies which quantified the magnitude and direction of bias mechanisms. A framework to guide epidemiologists in the development, implementation and reporting of simulation studies to quantify bias was developed. Simulation is a potent tool to the quantification of bias

    Barriers to hepatitis C virus elimination: treatment discontinuation, treatment failure, and reinfection

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    Background: Direct-acting antiviral (DAA) treatment is being scaled up to eliminate hepatitis C virus (HCV) as a major public health threat. Aims: The aim of this research was to assess potential barriers to HCV elimination in Australia, including DAA discontinuation, treatment failure, and HCV reinfection. Specific aims included assessing (1) reinfection incidence in prison; (2) real-world effectiveness of retreatment for reinfection and (3) treatment failure; (4) national trends in retreatment for reinfection and treatment failure; and (5) national trends in treatment discontinuation. Methods: In Chapter 2, HCV reinfection incidence was assessed in a prospective cohort of people treated for HCV in four prisons. In Chapters 3 and 4, the effectiveness of retreatment for reinfection and treatment failure were assessed using standard of care data from a national observational cohort that included a broad range of treatment settings. In Chapter 5, a machine learning model was developed and applied to national pharmaceutical administrative data to assess trends in retreatment for reinfection and treatment failure. In Chapter 6, treatment discontinuation trends were assessed in national pharmaceutical administrative data. Key Findings: High HCV reinfection (13/100 person-years) was observed in prisons. Retreatment for reinfection was highly effective (95%), but high losses to follow-up during treatment (25%) were observed. The effectiveness of retreatment for treatment failure (81%) was not impacted by treatment setting, supporting decentralisation of HCV care. A machine learning model with high predictive accuracy (96%) to classify retreatment reason was developed. When applied, an increasing national trend of retreatment for reinfection was observed. Half of retreatment for treatment failure was among individuals discontinuing treatment. National treatment discontinuation rates doubled between 2016-2021, rising to 15%, despite increasing use of simplified shorter duration DAA regimens. Conclusions: Retreatment of reinfection and treatment failure will be crucial to reduce HCV transmission and HCV-related morbidity and mortality. Retreatment can be effectively delivered through decentralised models of HCV care. Increasing trends of retreatment for reinfection and treatment discontinuation correspond with increasing treatment uptake among people who inject drugs. Additional strategies are needed to ensure vulnerable populations achieve and maintain HCV cure

    Out of sight, out of mind: accessibility for people with hidden disabilities in museums and heritage sites

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    As of 2020, an estimated 14.1 million residents of the United Kingdom reported a disability (DWP 2020). Within this population, approximately 6.1 million people have a hidden disability (Buhalis and Michopoulou 2011). These hidden disabilities range widely, from neurodiverse conditions like autism and dyslexia to long term chronic conditions such as fibromyalgia and arthritis. Due to the wide range of disabilities and their impact on a disabled person’s life, they have generally been underrepresented in accessibility studies. This thesis uncovers the accessibility needs of people with hidden disabilities, specifically in museums and heritage sites where they have heretofore mostly been overlooked. I utilise semi-structured interviews and correspondence with people with hidden disabilities, as well as participant-led experiences through three case study sites in Northern England, to understand the barriers they face. Their experiences help me expose the importance of passive accessibility – accessibility measures built directly into an exhibition design, such as adequate lighting and personal interpretation boards. Additionally, this thesis aims to understand the cultural forces that prevent or support accessibility-related improvements to such sites from taking place. By studying the cultural make-up of each case study organisation through ethnographic observations of the staff at these sites, institutional roadblocks to enacting accessibility-related adjustments are revealed. Specifically, the lack of communication at these sites presents a significant barrier to enacting accessibility suggestions from disabled visitors. Tying together the themes of active/passive accessibility and lack of communication is the theme of gaps in disability awareness, by which I mean that heritage organisations do not wilfully create these barriers to inclusion, and yet they create them still because they simply do not realise these things. Filling these gaps opens up countless possibilities for improving accessibility not only for people with hidden disabilities but for all visitors and staff at museums and heritage sites

    A model not a prophet:Operationalising patient-level prediction using observational data networks

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    Improving prediction model developement and evaluation processes using observational health data

    Current Insights on Lipid-Based Nanosystems

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    Lipid-based nanosystems, including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), cationic lipid nanoparticles, nanoemulsions, and liposomes, have been extensively studied to improve drug delivery through different administration routes. The main advantages of these systems are their ability to protect, transport, and control the release of lipophilic and hydrophilic molecules (either small-molecular-weight molecules or macromolecules); the use of generally recognized as safe (GRAS) excipients that minimize the toxicity of the formulations; and the possibility to modulate pharmacokinetics and enable the site-specific delivery of encapsulated payloads. In addition, the versatility of lipid-based nanosystems has further been demonstrated for the delivery of vaccines, the protection of active cosmetic ingredients, and the improvement of moisturizing properties of cosmetic formulations.Lipid-based nanosystems are well established and there are already different commercially approved formulations for various human disorders. This success has paved the way for the diversification of the pipeline of development, to address unmet medical needs for several indications, such as cancer, neurological disorders, and autoimmune, genetic, and infectious diseases.This Special Issue aims to update readers on the latest research on lipid-based nanosystems, both at the preclinical and clinical levels. A series of 15 articles (six reviews and nine studies) is presented, with authors from 12 different countries, showing the globality of the investigations that are being carried out in this area
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