Autonomic dysfunction in patients with advanced cancer; prevalence, clinical correlates and challenges in assessment

<p>Abstract</p> <p>Background</p> <p>The results of a small number of studies of autonomic function in patients with advanced cancer suggest that autonomic dysfunction (AD) is common. In other disease-specific groups this is associated with decreased survival, falls and symptoms such as postural hypotension, nausea, early satiety and fatigue. The contribution of AD to symptoms in advanced cancer is unknown.</p> <p>Methods</p> <p>We conducted a prospective cohort study designed to identify the risk factors for falls in patients with advanced cancer. Ambulant adult patients admitted consecutively to palliative care services were invited to participate. Participants underwent an assessment at baseline which included standard clinical tests of autonomic function, assessment of symptom severity, muscle strength, anthropometric measurements, walking speed, medication use, comorbidities and demographics. Information regarding survival was recorded ten months following cessation of recruitment. The clinical correlates of AD, defined as definite or severe dysfunction using Ewing's classification, were examined by univariate and multivariate logistic regression analysis. Survival analysis was conducted using Kaplan-Meier plots and the log rank test.</p> <p>Results</p> <p>Of 185 patients recruited, 45% were unable to complete all of the clinical tests of autonomic function. Non-completion was associated with scoring high on clinical indicators of frailty. It was possible to accurately classify 138/185 (74.6%) of participants as having either definite or severe versus normal, early or atypical AD: 110 (80%) had definite/severe AD. In logistic regression analysis, age (OR = 1.07 [95% CI; 1.03-1.1] <it>P </it>= 0.001) and increased severity of fatigue (OR = 1.26 [95% CI; 1.05-1.5] <it>p </it>= 0.016) were associated with having definite/severe AD. In analysis adjusted for age, median survival of participants with definite/severe AD was shorter than in those with normal/early/atypical classification (χ²= 4.3, <it>p </it>= 0.038).</p> <p>Conclusions</p> <p>Autonomic dysfunction is highly prevalent in patients with advanced cancer and is associated with increased severity of fatigue and reduced survival. Due to frailty, up to 45% of participants were unable to complete standard clinical tests of autonomic function. In order to further investigate the impact of AD and the therapeutic potential of treatment of AD in patients with advanced cancer, the validity of alternative novel methods of assessing autonomic function must be appraised.</p

Disabilities Moderate the Association between Neighbourhood Urbanity and Cognitive Health:Results from the Irish Longitudinal Study on Ageing

Background Geographical variations in cognitive health have been extensively explored, but the evidence on adult individuals with disabilities is inconclusive. While urban living is suggested as more cognitively stimulating than rural dwelling in epidemiological research, both rurality and urbanity can present barriers that may negatively impact cognitive health, the former due to limited accessibility to stimulation, and the latter because presenting environmental stressors. Objective To bridge this gap in the literature, we investigated geographical variations in multiple cognitive skills in adult age based on neighbourhood urbanity and having disabilities. Methods Data on global cognition, memory, speed of processing and executive functions, as well as reported functional limitations, was taken from 4,127 individuals aged 50+ participating in the first wave of The Irish Longitudinal Study on Ageing (TILDA). Neighbourhood urbanity was measured using Census data on population density. Multivariate regression analyses controlled for socio-demographic, health and lifestyle covariates. Results Residence in medium-high densely populated areas was significantly associated with better cognitive performance across all measures, after controlling for covariates. However, having disabilities was linked to worse global cognitive functioning (MoCA, p = .005), immediate recall (p = .022) and executive functions (CTT2, p = .009) in the least and most densely populated areas. Conclusions Living in urbanised areas may provide more mental stimulation than rural places; however, functional limitations moderate this association, suggesting potential environmental challenges both in rural and urban areas. Considering both individual and environmental circumstances can enrich investigations of geographical variations in cognitive health

Imaging in thick samples, a phased Monte Carlo radiation transfer algorithm

This work was supported by the EPSRC (Grant No. EP/K503162/1).Significance : Optical microscopy is characterized by the ability to get high resolution, below 1  μm, high contrast, functional and quantitative images. The use of shaped illumination, such as with lightsheet microscopy, has led to greater three-dimensional isotropic resolution with low phototoxicity. However, in most complex samples and tissues, optical imaging is limited by scattering. Many solutions to this issue have been proposed, from using passive approaches such as Bessel beam illumination to active methods incorporating aberration correction, but making fair comparisons between different approaches has proven to be challenging. Aim : We present a phase-encoded Monte Carlo radiation transfer algorithm (φMC) capable of comparing the merits of different illumination strategies or predicting the performance of an individual approach. Approach : We show that φMC is capable of modeling interference phenomena such as Gaussian or Bessel beams and compare the model with experiment. Results : Using this verified model, we show that, for a sample with homogeneously distributed scatterers, there is no inherent advantage to illuminating a sample with a conical wave (Bessel beam) instead of a spherical wave (Gaussian beam), except for maintaining a greater depth of focus. Conclusion : φMC is adaptable to any illumination geometry, sample property, or beam type (such as fractal or layered scatterer distribution) and as such provides a powerful predictive tool for optical imaging in thick samples.Publisher PDFPeer reviewe

Comparisons of disease cluster patterns, prevalence and health factors in the USA, Canada, England and Ireland

Abstract Background Identification of those who are most at risk of developing specific patterns of disease across different populations is required for directing public health policy. Here, we contrast prevalence and patterns of cross-national disease incidence, co-occurrence and related risk factors across population samples from the U.S., Canada, England and Ireland. Methods Participants (n = 62,111) were drawn from the US Health and Retirement Study (n = 10,858); the Canadian Longitudinal Study on Ageing (n = 36,647); the English Longitudinal Study of Ageing (n = 7938) and The Irish Longitudinal Study on Ageing (n = 6668). Self-reported lifetime prevalence of 10 medical conditions, predominant clusters of multimorbidity and their specific risk factors were compared across countries using latent class analysis. Results The U.S. had significantly higher prevalence of multimorbid disease patterns and nearly all diseases when compared to the three other countries, even after adjusting for age, sex, BMI, income, employment status, education, alcohol consumption and smoking history. For the U.S. the most at-risk group were younger on average compared to Canada, England and Ireland. Socioeconomic gradients for specific disease combinations were more pronounced for the U.S., Canada and England than they were for Ireland. The rates of obesity trends over the last 50 years align with the prevalence of eight of the 10 diseases examined. While patterns of disease clusters and the risk factors related to each of the disease clusters were similar, the probabilities of the diseases within each cluster differed across countries. Conclusions This information can be used to better understand the complex nature of multimorbidity and identify appropriate prevention and management strategies for treating multimorbidity across countries

Depression at Work, Authenticity in Question: Experiencing, Concealing and Revealing

Australia and the UK have both introduced policies to protect employees who experience mental illness, including depression. However, a better understanding of the issues workers face (e.g. sense of moral failure) is needed for the provision of appropriate and beneficial support. We analysed 73 interviews from the UK and Australia where narratives of depression and work intersected. Participants encountered difficulties in being (and performing as if) ‘authentic’ at work, with depression contributing to confusions about the self. The diffuse post-1960s imperative to ‘be yourself’ is experienced in conflicting ways: While some participants sought support from managers and colleagues (e.g. sick leave, back to work plans), many others put on a façade in an attempt to perform the ‘well’ and ‘authentic’ employee. We outline the contradictory forces at play for participants when authenticity and visibility are expected, yet moral imperatives to be good (healthy) employees are normative

StrokeCog Markov Model Projected Prevalent and Incident Cases of Stroke and Poststroke Cognitive Impairment to 2035 in Ireland

Background and Purpose: Cognitive impairment no dementia (CIND) and dementia are common stroke outcomes, with significant health and societal implications for aging populations. These outcomes are not included in current epidemiological models. We aimed to develop an epidemiological model to project incidence and prevalence of stroke, poststroke CIND and dementia, and life expectancy, in Ireland to 2035, informing policy and service planning. Methods: We developed a probabilistic Markov model (the StrokeCog model) applied to the Irish population aged 40 to 89 years to 2035. Data sources included official population and hospital-episode statistics, longitudinal cohort studies, and published estimates. Key assumptions were varied in sensitivity analysis. Results were externally validated against independent sources. The model tracks poststroke progression into health states characterized by no cognitive impairment, CIND, dementia, disability, stroke recurrence, and death. Results: We projected 69 051 people with prevalent stroke in Ireland in 2035 (22.0 per 1000 population [95% CI, 20.8-23.1]), with 25 274 (8.0 per 1000 population [95% CI, 7.1-9.0]) of those projected to have poststroke CIND, and 12 442 having poststroke dementia (4.0 per 1000 population [95% CI, 3.2-4.8]). We projected 8725 annual incident strokes in 2035 (2.8 per 1000 population [95% CI, 2.7-2.9]), with 3832 of these having CIND (1.2 per 1000 population [95% CI, 1.1-1.3]), and 1715 with dementia (0.5 per 1000 population [95% CI, 0.5-0.6]). Life expectancy for stroke survivors at age 50 was 23.4 years (95% CI, 22.3-24.5) for women and 20.7 (95% CI, 19.5-21.9) for men. Conclusions: This novel epidemiological model of stroke, poststroke CIND, and dementia draws on the best available evidence. Sensitivity analysis indicated that findings were robust to assumptions, and where there was uncertainty a conservative approach was taken. The StrokeCog model is a useful tool for service planning and cost-effectiveness analysis and is available for adaptation to other national contexts.Peer reviewe