2019 RD&E publications

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A summary list of all RD&E research outputs published or issued in 2019


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Now showing 1 - 5 of 367
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    Tip of the Iceberg: Assessing the Global Socioeconomic Costs of Alzheimer's Disease and Related Dementias and Strategic Implications for Stakeholders
    (IOS Press, 2019) Ballard, Clive
    While it is generally understood that Alzheimer's disease (AD) and related dementias (ADRD) is one of the costliest diseases to society, there is widespread concern that researchers and policymakers are not comprehensively capturing and describing the full scope and magnitude of the socioeconomic burden of ADRD. This review aimed to 1) catalogue the different types of AD-related socioeconomic costs described in the literature; 2) assess the challenges and gaps of existing approaches to measuring these costs; and 3) analyze and discuss the implications for stakeholders including policymakers, healthcare systems, associations, advocacy groups, clinicians, and researchers looking to improve the ability to generate reliable data that can guide evidence-based decision making. A centrally emergent theme from this review is that it is challenging to gauge the true value of policies, programs, or interventions in the ADRD arena given the long-term, progressive nature of the disease, its insidious socioeconomic impact beyond the patient and the formal healthcare system, and the complexities and current deficiencies (in measures and real-world data) in accurately calculating the full costs to society. There is therefore an urgent need for all stakeholders to establish a common understanding of the challenges in evaluating the full cost of ADRD and define approaches that allow us to measure these costs more accurately, with a view to prioritizing evidence-based solutions to mitigate this looming public health crisis.
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    Epigenome-wide Association Study of Attention-Deficit/Hyperactivity Disorder Symptoms in Adults
    (Elsevier Science, 2019-10-15) Hannon, Eilis; Mill, Jonathan
    Background: Previous studies have reported associations between attention-deficit/hyperactivity disorder symptoms and DNA methylation in children. We report the first epigenome-wide association study meta-analysis of adult attention-deficit/hyperactivity disorder symptoms, based on peripheral blood DNA methylation (Infinium HumanMethylation450K array) in three population-based adult cohorts. Methods: An epigenome-wide association study was performed in the Netherlands Twin Register (N = 2258, mean age 37 years), Dunedin Multidisciplinary Health and Development Study (N = 800, age 38 years), and Environmental Risk Longitudinal Twin Study (N = 1631, age 18 years), and results were combined through meta-analysis (total sample size N = 4689). Region-based analyses accounting for the correlation between nearby methylation sites were also performed. Results: One epigenome-wide significant differentially methylated position was detected in the Dunedin study, but meta-analysis did not detect differentially methylated positions that were robustly associated across cohorts. In region-based analyses, six significant differentially methylation regions (DMRs) were identified in the Netherlands Twin Register, 19 in the Dunedin study, and none in the Environmental Risk Longitudinal Twin Study. Of these DMRs, 92% were associated with methylation quantitative trait loci, and 68% showed moderate to large blood-brain correlations for DNA methylation levels. DMRs included six nonoverlapping DMRs (three in the Netherlands Twin Register, three in the Dunedin study) in the major histocompatibility complex, which were associated with expression of genes in the major histocompatibility complex, including C4A and C4B, previously implicated in schizophrenia. Conclusions: Our findings point at new candidate loci involved in immune and neuronal functions that await further replication. Our work also illustrates the need for further research to examine to what extent epigenetic associations with psychiatric traits depend on characteristics such as age, comorbidities, exposures, and genetic background.
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    Interventions to improve the mental health of children and young people with long-term physical conditions: linked evidence syntheses
    (NIHR Journals Library, 2019-05) Moore, D. A.; Nunns, M.; Rogers, M.; Ford, T.; Garside, R.; Ukoumunne, O. C.; Anderson, R.; Dickens, C.; Logan, Stuart; Thompson Coon, J.
    Background: Although mental health difficulties can severely complicate the lives of children and young people (CYP) with long-term physical conditions (LTCs), there is a lack of evidence about the effectiveness of interventions to treat them. Objectives: To evaluate the clinical effectiveness and cost-effectiveness of interventions aiming to improve the mental health of CYP with LTCs (review 1) and explore the factors that may enhance or limit their delivery (review 2). Data sources: For review 1, 13 electronic databases were searched, including MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Science Citation Index. For review 2, MEDLINE, PsycINFO and CINAHL were searched. Supplementary searches, author contact and grey literature searches were also conducted. Review methods: The first systematic review sought randomised controlled trials (RCTs) and economic evaluations of interventions to improve elevated symptoms of mental ill health in CYP with LTCs. Effect sizes for each outcome were calculated post intervention (Cohen's d). When appropriate, random-effects meta-analyses produced pooled effect sizes (d). Review 2 located primary qualitative studies exploring experiences of CYP with LTCs, their families and/or practitioners, regarding interventions aiming to improve the mental health and well-being of CYP with LTCs. Synthesis followed the principles of metaethnography. An overarching synthesis integrated the findings from review 1 and review 2 using a deductive approach. End-user involvement, including topic experts and CYP with LTCs and their parents, was a feature throughout the project. Results: Review 1 synthesised 25 RCTs evaluating 11 types of intervention, sampling 12 different LTCs. Tentative evidence from seven studies suggests that cognitive-behavioural therapy interventions could improve the mental health of CYP with certain LTCs. Intervention-LTC dyads were diverse, with few opportunities to meta-analyse. No economic evaluations were located. Review 2 synthesised 57 studies evaluating 21 types of intervention. Most studies were of individuals with cancer, a human immunodeficiency virus (HIV) infection or mixed LTCs. Interventions often aimed to improve broader mental health and well-being, rather than symptoms of mental health disorder. The metaethnography identified five main constructs, described in an explanatory line of argument model of the experience of interventions. Nine overarching synthesis categories emerged from the integrated evidence, raising implications for future research. Limitations: Review 1 conclusions were limited by the lack of evidence about intervention effectiveness. No relevant economic evaluations were located. There were no UK studies included in review 1, limiting the applicability of findings. The mental health status of participants in review 2 was usually unknown, limiting comparability with review 1. The different evidence identified by the two systematic reviews challenged the overarching synthesis. Conclusions: There is a relatively small amount of comparable evidence for the effectiveness of interventions for the mental health of CYP with LTCs. Qualitative evidence provided insight into the experiences that intervention deliverers and recipients valued. Future research should evaluate potentially effective intervention components in high-quality RCTs integrating process evaluations. End-user involvement enriched the project.
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    The Incidence of Recorded Delirium Episodes Before and After Dementia Diagnosis: Differences Between Dementia With Lewy Bodies and Alzheimer's Disease
    (Elsevier Science, 2019-05) Ballard, Clive
    Objectives: To describe the incidence of delirium recording before and after a diagnosis of dementia is established in patients with dementia with Lewy bodies (DLB) and compare findings to a matched cohort of patients with Alzheimer's disease (AD). Design: Retrospective cohort study. Setting and participants: A cohort of patients with dementia from a large mental health and dementia care database in South London, linked to hospitalization and mortality data. We identified 194 patients with DLB and 1:4 matched these with 776 patients diagnosed with AD on age, gender, and cognitive status. Measures: We identified delirium episodes recorded in mental health and hospital records from 1 year before to 1 year after dementia diagnosis. Using dementia diagnosis as an index date we additionally followed patients until first episode of delirium, death or a censoring point without restricting the observation period. Results: Patients with DLB had significantly more episodes of delirium recorded in the year before dementia diagnosis than patients with AD (incidence rate 17.6 vs 3.2 per 100 person-years; P < .001). Whereas the incidence of recording of delirium episodes reduced substantially in patients with DLB after dementia diagnosis, it remained significantly higher than in patients with AD (incidence rate 6.2 vs 2.3 per 100 person-years; P = .032). Cox regression models indicate that patients with DLB remain at a higher risk of delirium than patients with AD after a dementia diagnosis. Conclusions/relevance: Establishing a diagnosis of dementia reduces episodes classified as delirium in patients with DLB and might lead to fewer potentially harmful interventions such as hospitalization or use of antipsychotic medication.
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    Telomere length and aging-related outcomes in humans: A Mendelian randomization study in 261,000 older participants
    (Wiley, 2019-12) Pilling, L. C.; Melzer, David
    Inherited genetic variation influencing leukocyte telomere length provides a natural experiment for testing associations with health outcomes, more robust to confounding and reverse causation than observational studies. We tested associations between genetically determined telomere length and aging-related health outcomes in a large European ancestry older cohort. Data were from n = 379,758 UK Biobank participants aged 40-70, followed up for mean of 7.5 years (n = 261,837 participants aged 60 and older by end of follow-up). Thirteen variants strongly associated with longer telomere length in peripheral white blood cells were analyzed using Mendelian randomization methods with Egger plots to assess pleiotropy. Variants in TERC, TERT, NAF1, OBFC1, and RTEL1 were included, and estimates were per 250 base pairs increase in telomere length, approximately equivalent to the average change over a decade in the general white population. We highlighted associations with false discovery rate-adjusted p-values smaller than .05. Genetically determined longer telomere length was associated with lowered risk of coronary heart disease (CHD; OR = 0.95, 95% CI: 0.92-0.98) but raised risk of cancer (OR = 1.11, 95% CI: 1.06-1.16). Little evidence for associations were found with parental lifespan, centenarian status of parents, cognitive function, grip strength, sarcopenia, or falls. The results for those aged 60 and older were similar in younger or all participants. Genetically determined telomere length was associated with increased risk of cancer and reduced risk of CHD but little change in other age-related health outcomes. Telomere lengthening may offer little gain in later-life health status and face increasing cancer risks.