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Aim: To investigate the association between cardiovascular health metrics defined by Life's Essential 8 (LE8) scores and vascular complications among individuals with type 2 diabetes (T2D). Materials and Methods: This prospective study included 11 033 participants with T2D, all devoid of macrovascular diseases (including cardiovascular and peripheral artery disease) and microvascular complications (e.g. diabetic retinopathy, neuropathy and nephropathy) at baseline from the UK Biobank. The LE8 score comprised eight metrics: smoking, body mass index, physical activity, non‐high‐density lipoprotein cholesterol, blood pressure, glycated haemoglobin, diet and sleep duration. Cox proportional hazards models were established to assess the associations of LE8 scores with incident macrovascular and microvascular complications. Results: During a median follow‐up of 12.1 years, we identified 1975 cases of incident macrovascular diseases and 1797 cases of incident microvascular complications. After adjusting for potential confounders, each 10‐point increase in the LE8 score was associated with an 18% lower risk of macrovascular diseases and a 15% lower risk of microvascular complications. Comparing individuals in the highest and lowest quartiles of LE8 scores revealed hazard ratios of 0.55 (95% confidence interval 0.47‐0.62) for incident macrovascular diseases, and 0.61 (95% confidence interval 0.53‐0.70) for incident microvascular complications. This association remained robust across a series of sensitivity analyses and nearly all subgroups. Conclusion: Higher LE8 scores were associated with a lower risk of incident macrovascular and microvascular complications among individuals with T2D. These findings underscore the significance of adopting fundamental strategies to maintain optimal cardiovascular health and curtail the risk of developing diabetic vascular complications. [ABSTRACT FROM AUTHOR]

Background: Air pollution has been recognised as a potential risk factor for dementia. Yet recent epidemiological research shows mixed evidence. The aim of this study is to investigate the longitudinal associations between ambient air pollution exposure and dementia in older people across five urban and rural areas in the UK. Methods: This study was based on two population-based cohort studies of 11329 people aged ≥ 65 in the Cognitive Function and Ageing Study II (2008–2011) and Wales (2011–2013). An algorithmic diagnosis method was used to identify dementia cases. Annual concentrations of four air pollutants (NO2, O3, PM10, PM2.5) were modelled for the year 2012 and linked via the participants' postcodes. Multistate modelling was used to examine the effects of exposure to air pollutants on incident dementia incorporating death and adjusting for sociodemographic factors and area deprivation. A random-effect meta-analysis was carried out to summarise results from the current and nine existing cohort studies. Results: Higher exposure levels of NO2 (HR: 1.04; 95% CI: 0.94, 1.14), O3 (HR: 0.90; 95% CI: 0.70, 1.15), PM10 (HR: 1.17; 95% CI: 0.86, 1.58), PM2.5 (HR: 1.41; 95% CI: 0.71, 2.79) were not strongly associated with dementia in the two UK-based cohorts. Inconsistent directions and strengths of the associations were observed across the two cohorts, five areas, and nine existing studies. Conclusions: In contrast to the literature, this study did not find clear associations between air pollution and dementia. Future research needs to investigate how methodological and contextual factors can affect evidence in this field and clarity the influence of air pollution exposure on cognitive health over the lifecourse. [ABSTRACT FROM AUTHOR]

Although GWASs have been conducted to investigate genetic variation of bladder tumorigenesis, little is known about genetic interactions that may influence bladder cancer (BC) risk. By leveraging large‐scale participants from UK Biobank, we established a discovery database with 4000 Caucasian participants (2000 cases vs 2000 non‐cases), a database with 1648 Caucasian participants (824 cases vs 824 non‐cases) and 856 non‐Caucasian participants (428 cases vs 428 non‐cases) as validation. We then performed a genome‐wide SNP‐SNP interaction investigation related to BC risk based a machine learning approach (ie, GenEpi). Moreover, we used the selected interactions to build a BC screening model with an integrated interaction‐empowered polygenic risk score (iPRS) based on Cox proportional hazard model. With Bonferroni correction, we identified 10 statistically significant pairs of SNPs, which located in 17 chromosomes. Of these, four SNP‐SNP interactions were found to be positively associated with BC risk among Caucasian participants (ORs 1.57‐2.03), while six SNP‐SNP interactions showed negatively associated with BC risk (ORs 0.54‐0.65). Only four of the SNP‐SNP interactions were consistently identified in non‐Caucasian participants located in ST7L‐ADSS2, FHIT‐CHDH, LARP4B‐LHPP and RBFOX3‐MPRIP. In addition, the iPRS showed a HR of 1.81 (95% CI: 1.46‐2.09) compared the highest tertile to the lowest tertile, with an enhanced AUC (0.91; 95% CI:0.85‐0.97) than PRS (AUC: 0.86; 95% CI:0.76‐0.95; P‐DeLong test = 2.2 × 10−4). In summary, this study identified several important SNP‐SNP interactions for BC risk, and developed an iPRS model for BC screening, which may help to identify the people at high‐risk state of BC before early manifestation. [ABSTRACT FROM AUTHOR]

Cardiorespiratory fitness is an established predictor of metabolic disease and mortality. Fitness is directly measured as maximal oxygen consumption (VO2max), or indirectly assessed using heart rate responses to standard exercise tests. However, such testing is costly and burdensome because it requires specialized equipment such as treadmills and oxygen masks, limiting its utility. Modern wearables capture dynamic real-world data which could improve fitness prediction. In this work, we design algorithms and models that convert raw wearable sensor data into cardiorespiratory fitness estimates. We validate these estimates' ability to capture fitness profiles in free-living conditions using the Fenland Study (N=11,059), along with its longitudinal cohort (N = 2675), and a third external cohort using the UK Biobank Validation Study (N = 181) who underwent maximal VO2max testing, the gold standard measurement of fitness. Our results show that the combination of wearables and other biomarkers as inputs to neural networks yields a strong correlation to ground truth in a holdout sample (r = 0.82, 95CI 0.80–0.83), outperforming other approaches and models and detects fitness change over time (e.g., after 7 years). We also show how the model's latent space can be used for fitness-aware patient subtyping paving the way to scalable interventions and personalized trial recruitment. These results demonstrate the value of wearables for fitness estimation that today can be measured only with laboratory tests. [ABSTRACT FROM AUTHOR]

Depression is a common condition in dementia and has a substantial impact on quality of life and wellbeing. There is limited evidence on how depressive symptoms in the person with dementia impact on the carer, and vice versa. The aim of this study is to investigate dyadic relationships between depressive symptoms and capability to live well in both people with dementia and their carers and to examine whether people with dementia who do not have a carer are more vulnerable to the impact of depressive symptoms than those who have a carer. Using a large cohort study of 1547 community-dwelling people with mild to moderate dementia and 1283 carers in Great Britain, a Bayesian analysis framework was developed to incorporate dyads (N = 981), people with dementia whose carers did not participate (N = 127), people with dementia who did not have a carer (N = 137), and dyads with missing data (N = 302) and estimate actor and partner relationships between depressive symptoms and capability to live well, which was expressed as a latent factor derived from measures of quality of life, life satisfaction and wellbeing. Depressive symptoms in people with dementia and carers had negative associations with capability to live well both for the individual and for the partner. Compared to those who had a carer, depressive symptoms had a greater impact on capability to live well in people with dementia who did not had a carer. The impact of depression may extend beyond the person experiencing the symptoms. Future interventions for depressive symptoms should utilise this potential wider impact to understand and optimise treatment effects. [ABSTRACT FROM AUTHOR]

Background a large number of studies have explored factors related to self- and informant ratings of quality of life in people with dementia, but many studies have had relatively small sample sizes and mainly focused on health conditions and dementia symptoms. The aim of this study is to compare self- and informant-rated quality of life, life satisfaction and well-being, and investigate the relationships of the two different rating methods with various social, psychological and health factors, using a large cohort study of community-dwelling people with dementia and carers in Great Britain. Methods this study included 1,283 dyads of people with mild-to-moderate dementia and their primary carers in the Improving the experience of Dementia and Enhancing Active Life study. Multivariate modelling was used to investigate associations of self- and informant-rated quality of life, life satisfaction and well-being with factors in five domains: psychological characteristics and health; social location; capitals, assets and resources; physical fitness and health; and managing everyday life with dementia. Results people with dementia rated their quality of life, life satisfaction and well-being more highly than did the informants. Despite these differences, the two approaches had similar relationships with social, psychological and physical health factors in the five domains. Conclusion although self- and informant ratings differ, they display similar results when focusing on factors associated with quality of life, life satisfaction and well-being. Either self- or informant ratings may offer a reasonable source of information about people with dementia in terms of understanding associated factors. [ABSTRACT FROM AUTHOR]

Protecting stone buildings from weathering and decay is a major challenge in the conservation of built heritage. Most of the stone consolidants currently available are well suited to silicate stones, but are less compatible with limestone. In this paper we present for the first time the results over a 4-year period of various consolidation treatments carried out using nanolime on 6 of the most representative and significant stones used in historic buildings in the United Kingdom. Tests investigated the influence of stone type, environmental conditions and pre-treatments on the effectiveness of the consolidation treatment. A comprehensive and rigorous testing programme was carried out to evaluate the short (12 weeks) and longer-term (4 years) effects. Stone samples were characterised before and after treatment using light and electron microscopy, sorptivity tests and a novel methodology employing drilling resistance to interrogate the near surface effects. Results show that for some of the stones, such as Clunch and Bath Stone, the positive effect of the treatment with nanolime is noticeable after 4 years since application. However, results for other stones such as Portland and magnesian limestone showed that the initial beneficial effect of the treatment is reduced after 4 years. Nanolime treatment of Ham Stone produced an unnoticeable effect on the continuous natural reduction of the drilling resistance of the specimen over time. The results presented are of immense value to conservators as they provide essential guidance on the most appropriate repair approach. Impact to the conservation industry will be to avoid the use of nanolime on stones where there is no perceivable benefit, reducing the risk of adverse effects, including potential damage to buildings. In additional costs will be saved which might otherwise have been spent on ineffective treatments. [ABSTRACT FROM AUTHOR]

To examine the patterns of use of potentially interacting supplement–drug pairs in adults with type 2 diabetes (T2D) in real-world settings, and to explore the impact of potentially interacting supplement–drug pairs on downstream outcomes. Potentially interacting supplement–drug pairs were identified from four tertiary databases. We categorized the potential pharmacodynamic interactions into different clinical types according to their related outcomes and explored their associations with incident outcomes using Cox models. 26,394 participants with T2D in the UK Biobank were included. Half (48.5 %) were supplement users, of whom 85.0 % were taking potentially interacting supplement–drug pairs. The potential pharmacodynamic interactions were related to various clinical outcomes, including reducing the effects of glucose-lowering drugs (50.7 %), hypotension (49.8 %), bleeding (50.4 %) and hepatotoxicity (34.8 %). Exploratory analyses found that the use of potentially interacting supplement–drug pairs was associated with incident hepatic diseases (hazard ratio = 1.26, 95 % confidence interval 1.10–1.44, P < 0.001). Real-world data suggests that most adults with T2D who concurrently used supplements and drugs were on potentially interacting supplement-drug combinations, with the potential of causing adverse outcomes such as incident hepatic diseases. Clinicians should communicate with patients and assess the potential risk of supplement–drug interactions in clinical settings. [ABSTRACT FROM AUTHOR]

The article presents a study examining the transitional/adaptation challenges being faced by foreign-educated nurses (FENs) in the U.S. healthcare system from multiple stakeholders including clinical educators, preceptors, and the FENs themselves. The study found that five of the six FENs surveyed were unable to take advantage of the English as a second language (ESL) classes and accent reduction classes offered by the hospitals because of other competing or more pressing life demands. It also found that it was believed by the preceptors that the two main issues influencing the adaptation of the FENs were 'learning the system' and 'learning the American culture.'

Background: This study examines the association between traditional cardiovascular health (CVH) metrics and major adverse cardiovascular events (MACE) incidence in individuals with diverse sleep patterns., Methods and Results: We analyzed data from 208 621 participants initially free of cardiovascular disease (CVD) in the UK Biobank study. Sleep patterns were assessed using scores for chronotype, duration, insomnia, snoring, and daytime dozing. Traditional CVH scores were derived from the Life's Simple 7 metrics. Cox proportional hazards multivariate regression assessed associations between distinct combinations of CVH and sleep scores and MACE, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality. Over a mean follow-up of 12.73 years, 9253 participants experienced incident MACE. Individuals with both a healthy sleep pattern and ideal CVH levels had the lowest MACE risk compared with those with a poor sleep pattern and poor CVH levels (hazard ratio, 0.306 [95% CI, 0.257-0.365]; P <0.001). Elevated CVH scores were associated with a reduced risk of MACE across different sleep patterns. Similar trends were observed for individual MACE components, heart failure, and all-cause mortality. These findings remained robust in sensitivity analyses and across various subgroups., Conclusions: In individuals without known CVD, maintaining a favorable sleep pattern and achieving optimal CVH levels, as measured by traditional metrics, were associated with the lowest MACE risk. Enhanced CVH significantly reduced CVD risk, even in individuals with a poor sleep pattern. These results emphasize the importance of considering multiple dimensions of sleep health alongside CVH to mitigate CVD risk., Registration: URL: https://www.ukbiobank.ac.uk; Unique identifier: 91090.

Dementia has been recognised as a key challenge in many ageing societies across the world. Several population-based studies have been developed to investigate dementia and cognitive ageing from perspectives of biology, health, psychology and social sciences. However, there is a need to provide a better understanding of 'contexts', the circumstance where these ageing populations existed, and heterogeneity within and across the populations in different time and places. In this article, we summarise some examples of earlier population-based studies undertaken by our research groups in England and Wales and their contribution to the epidemiology of dementia, neuropathology, cognitive and mental health in older age. We also describe how these studies illustrated variation among ageing populations and changes in their health conditions across time and place. These findings highlight the contribution that population-based studies can make, along with the vital to incorporate contexts in ageing research. A lifecourse approach within social context is needed to integrate life experiences, social circumstances, and multiple dimensions of cognition, functioning, physical health and wellbeing over the ageing process. We also discuss how evidence from population-based studies can support various international initiatives on dementia, healthy ageing and Sustainable Development Goals and facilitate tailored approaches for diverse populations across global societies.

Background: A growing number of studies have explored how features of the neighbourhood environment can be related to cognitive health in later life. Yet few have focused on low- and middle-income countries and compared the results across different settings. The aim of this study is to investigate the cross-sectional associations between neighbourhood amenities and dementia in older people from high-, middle- and low-income countries., Methods: This study was based on two population-based cohort studies of people aged≥65: the Cognitive Function and Ageing Study II (CFAS II) in UK (N = 4955) and a subset of the 10/66 study in China, Dominican Republic and Mexico (N = 3386). In both cohorts, dementia was assessed using the Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy (GMS-AGECAT) algorithm. The 10/66 dementia diagnostic algorithm was also used as an additional criterion in the 10/66 study. Publicly accessible databases, Google Maps and Open Street Map, were used to obtain geographic information system data on distance to neighbourhood amenities, including lifestyle (cafés, libraries, movie theatres, parks), daily life (post offices, convenience stores), healthcare (hospitals, pharmacies) and percentages of local green and blue spaces within 400 and 800 m of participants' residences. Multilevel logistic regression was used to investigate the associations between these environmental features and dementia adjusting for sociodemographic factors and self-rated health., Results: Living far from daily life amenities was associated with higher odds of dementia in both CFAS II (1.47; 95% CI: 0.96, 2.24) and the 10/66 study (1.53; 95% CI: 1.15, 2.04), while living far from lifestyle (1.50; 95% CI: 1.13, 1.99) and healthcare amenities (1.32; 95% CI: 0.93, 1.87) was associated with higher odds of dementia only in the 10/66 study. A high availability of local green and blue spaces was not associated with dementia in either cohort yet living far from public parks was associated with lower odds of dementia in CFAS II (0.64; 95% CI: 0.41, 1.00)., Conclusions: The different relationships across cohorts may indicate a varying role for local amenities in diverse settings. Future research may investigate mechanisms related to these differences and social, cultural and historical influences on the interaction between neighbourhood amenities and older people.

Introduction: Understanding key influences on outcomes for caregivers of people with dementia is hampered by inconsistent conceptualization and measurement of outcomes and limited evidence about the relative impact of different variables. We aimed to address these issues., Methods: We analyzed data from 1283 caregivers of community-dwelling individuals with mild-to-moderate dementia in the Improving the experience of Dementia and Enhancing Active Life cohort study. We generated a "living well" latent factor from measures of quality of life, satisfaction with life, and well-being. We used structural equation modelling to derive latent variables for 7 domains reflecting caregivers' perceptions of their personal resources and experiences, and to examine the associations with caregivers' perceptions of their capability to "live well.", Results: The domain of psychological characteristics and psychological health was most strongly related to living well [2.53; 95% confidence interval (CI), 2.08-2.97], followed by physical fitness and physical health (1.48; 95% CI, 1.04-1.91) and experiencing caregiving (1.34; 95% CI, 0.99-1.70). Social capitals, assets and resources (0.68; 95% CI, 0.35-1.00) and relationship with the person with dementia (-0.22; 95% CI, -0.41 to -0.03) had smaller, significant associations. Social location (0.28; 95% CI, -0.33 to 0.89) and managing everyday life with dementia (0.06; 95% CI, -0.15 to 0.28) were not significantly associated with living well., Discussion: These findings demonstrate the importance of supporting caregivers' psychological and physical health and their ability to develop and maintain positive coping strategies, as well as enabling them to maintain vital social capitals, assets and resources.

Introduction: We aimed to better understand what predicts the capability to "live well" with dementia by identifying the relative contribution of life domains associated with the subjective experience of living well., Methods: We analyzed data from 1547 individuals with mild-to-moderate dementia in the IDEAL cohort. We generated a "living well" latent factor from measures of quality of life, satisfaction with life, and well-being. We used multivariate modeling to identify variables related to living well measures and structural equation modeling to derive latent variables for 5 life domains and to examine the associations of these domains with living well., Results: All 5 domains were individually associated with living well. When modeled together, the psychological characteristics and psychological health domain was the only independent predictor of living well [effect size, 3.55; 95% confidence interval (CI): 2.93-4.17], and effect sizes were smaller for physical fitness and physical health (1.23, 95% CI: -0.10 to 2.58), social capitals, assets and resources (0.67; 95% CI: -0.04 to 1.38), managing everyday life with dementia (0.33; 95% CI: -0.06 to 0.71), and social location (0.08; 95% CI: -2.10 to 2.26)., Discussion: Psychological resources, and the social, environmental, and physical factors that underpin positive psychological states, are potentially important targets for interventions and initiatives that aim to improve the experience of living with dementia.

Objectives: Area level factors, such as deprivation and urban/rural settings, have been associated with variation in local resources and services and health inequality in later life. The aim of this study is to investigate the potential impact of deprivation and urban/rural areas on capability to live well with dementia and to examine whether availability of informal carers modified the associations., Methods: The analysis was based on a large cohort study of 1547 community-dwelling people with dementia across Great Britain. Quality of life, life satisfaction, and well-being were measured as indices of "living well." Multivariate modelling was used to investigate differences in living well measures across deprivation quintiles and urban/rural areas adjusting for sociodemographic factors and number of comorbidities and stratifying by three groups: those living with a carer, those with a noncoresident carer and those without a carer., Results: Negative dose-response relationships between deprivation and measures of quality of life (-2.12; 95% CI: -3.52, -0.73), life satisfaction (-1.27; 95% CI: -2.70, 0.16), and well-being (-5.24; 95% CI: -10.11, -0.36) were found in participants living with a carer. The associations were less clear in those with a noncoresident carer and those without a carer but these two groups generally reported lower scores on living well indicators than participants living with a carer. There was no urban/rural difference., Conclusions: The findings suggest inequalities in living well with dementia according to levels of deprivation. Additional resources are needed to improve postdiagnostic care in highly deprived areas and support those who have no informal carer., (© 2018 John Wiley & Sons, Ltd.)

Background: The heterogeneity of symptoms across dementia subtypes has important implications for clinical practice and dementia research. Variation in subtypes and associated symptoms may influence the capability to live well for people with dementia and carers. The aim of this study is to investigate the potential impact of dementia subtypes on the capability to live well for both people with dementia and their carers., Methods: The analysis was based on the 1283 dyads of community-dwelling people with dementia and carers in the Improving the experience of Dementia and Enhancing Active Life (IDEAL) project, a large cohort study in Great Britain. Capability to live well was defined using three measures: quality of life, life satisfaction and wellbeing. Structural equation modelling was used to investigate capability to live well in seven dementia subtypes: Alzheimer's disease (AD), Vascular dementia (VaD), mixed AD/VaD, frontotemporal dementia (FTD), Parkinson's disease dementia (PDD), Lewy body dementia (LBD) and unspecified/other, accounting for dyadic data structure and adjusting for age and sex, type of relationship between person with dementia and their carer and the number of chronic conditions., Results: The major subtypes in this study population were AD (56%), VaD (11%) and mixed AD/VaD (21%). Compared to participants with AD, people with non-AD subtypes generally reported a lower capability to live well. Carers for people with PDD (- 1.71; 95% confidence interval (CI) - 3.24, - 0.18) and LBD (- 2.29; 95% CI - 3.84, - 0.75) also reported a lower capability to live well than carers for people with AD. After adjusting for demographic factors and comorbidity, PDD (- 4.28; 95% CI - 5.65, - 2.91) and LBD (- 3.76; 95% CI - 5.14, - 2.39) continued to have the strongest impact on both people with dementia and their carers., Conclusions: This study suggests a variation in capability to live well across dementia subtypes. It is important for care providers to consider different needs across subtypes. Health professionals who provide post-diagnostic support may need to pay more attention to the complex needs of people living with PDD and LBD and their carers.