Factors that impact on the quality of life of intestinal failure patients treated with home parenteral nutrition: protocol for a multicentre, longitudinal observational study

\ua9 2024 BMJ Publishing Group. All rights reserved. Background: Home parenteral nutrition (HPN) refers to the intravenous administration of macronutrients, micronutrients and fluid. The aims of treatment are to increase survival and improve quality of life (QoL). However, patients struggle with physiological symptoms, time-consuming invasive therapy and an increased occurrence of depression and social isolation. Our aim is to understand how HPN impacts the QoL of patients, and the contribution played by the complications of treatment, for example, liver disease. Methods and analysis: A multicentre, longitudinal, observational study will be conducted using routinely collected clinical data. Participants will also be asked to complete three QoL questionnaires (EuroQol-5 Dimensions, Short Form 36 and HPN-QoL) at baseline and 12 months. The primary outcome is mean change in QoL scores over 12 months. Secondary outcomes include how factors including liver function, gut microbiota, number of infusions of PN per week, nutritional composition of PN and nutritional status impact on QoL scores. Ethics and dissemination: Ethical approval was obtained from HRA and Health and Care Research Wales Research Ethics Committee (21/SC/0316). The study was eligible for portfolio adoption, Central Portfolio Management System ID 50506. Results will be disseminated through peer-reviewed scientific journals and presented at national and international meetings

Bioinformatic interrogation of expression array data to identify nutritionally regulated genes potentially modulated by DNA methylation

DNA methylation occurs at CpG dinucleotide sites within the genome and is recognised as one of the mechanisms involved in regulation of gene expression. CpG sites are relatively underrepresented in the mammalian genome, but occur densely in regions called CpG islands (CGIs). CGIs located in the promoters of genes inhibit transcription when methylated by impeding transcription factor binding. Due to the malleable nature of DNA methylation, environmental factors are able to influence promoter CGI methylation patterns and thus influence gene expression. Recent studies have provided evidence that nutrition (and other environmental exposures) can cause altered CGI methylation but, with a few exceptions, the genes influenced by these exposures remain largely unknown. Here we describe a novel bioinformatics approach for the analysis of gene expression microarray data designed to identify regulatory sites within promoters of differentially expressed genes that may be influenced by changes in DNA methylation

Healthy life gains in South Australia 1999-2008: analysis of a local Burden of Disease series

BACKGROUND: The analysis describes trends in the levels and social distribution of total life expectancy and healthy life expectancy in South Australia from 1999 to 2008. METHODS: South Australian Burden of Disease series for the period 1999-2001 to 2006-2008 and across statistical local areas according to relative socioeconomic disadvantage were analyzed for changes in total life expectancy and healthy life expectancy by sex and area level disadvantage, with further decomposition of healthy life expectancy change by age, cause of death, and illness. RESULTS: Total life expectancy at birth increased in South Australia for both sexes (2.0 years [2.6%] among males; 1.5 years [1.8%] among females). Healthy life expectancy also increased (1.4 years [2.1%] among males; 1.2 years [1.5%] among females). Total life and healthy life expectancy gains were apparent in all socioeconomic groups, with the largest increases in areas of most and least disadvantage. While the least disadvantaged areas consistently had the best health outcomes, they also experienced the largest increase in the amount of life expectancy lived with disease and injury-related illness. CONCLUSIONS: While overall gains in both total life and healthy life expectancy were apparent in South Australia, gains were greater for total life expectancy. Additionally, the proportion of expected life lived with disease and injury-related illness increased as disadvantage decreased. This expansion of morbidity occurred in both sexes and across all socio-economic groups. This analysis outlines the continuing improvements to population health outcomes within South Australia. It also highlights the challenge of reducing population morbidity so that gains to healthy life match those of total life expectancy.David Banham, Tony Woollacott and John Lync

Nutritional factors and gender influence age-related DNA methylation in the human rectal mucosa

Aberrant methylation of CpG islands (CGI) occurs in many genes expressed in colonic epithelial cells, and may contribute to the dysregulation of signalling pathways associated with carcinogenesis. This cross-sectional study assessed the relative importance of age, nutritional exposures and other environmental factors in the development of CGI methylation. Rectal biopsies were obtained from 185 individuals (84 male, 101 female) shown to be free of colorectal disease, and for whom measurements of age, body size, nutritional status and blood cell counts were available. We used quantitative DNA methylation analysis combined with multivariate modelling to investigate the relationships between nutritional, anthropometric and metabolic factors and the CGI methylation of 11 genes, together with LINE-1 as an index of global DNA methylation. Age was a consistent predictor of CGI methylation for 9/11 genes but significant positive associations with folate status and negative associations with vitamin D and selenium status were also identified for several genes. There was evidence for positive associations with blood monocyte levels and anthropometric factors for some genes. In general, CGI methylation was higher in males than in females and differential effects of age and other factors on methylation in males and females were identified. In conclusion, levels of age-related CGI methylation in the healthy human rectal mucosa are influenced by gender, the availability of folate, vitamin D and selenium, and perhaps by factors related to systemic inflammatio

How primary care can contribute to good mental health in adults.

The need for support for good mental health is enormous. General support for good mental health is needed for 100% of the population, and at all stages of life, from early childhood to end of life. Focused support is needed for the 17.6% of adults who have a mental disorder at any time, including those who also have a mental health problem amongst the 30% who report having a long-term condition of some kind. All sectors of society and all parts of the NHS need to play their part. Primary care cannot do this on its own. This paper describes how primary care practitioners can help stimulate such a grand alliance for health, by operating at four different levels - as individual practitioners, as organisations, as geographic clusters of organisations and as policy-makers

Deriving utility scores for co-morbid conditions: a test of the multiplicative model for combining individual condition scores

BACKGROUND: The co-morbidity of health conditions is becoming a significant health issue, particularly as populations age, and presents important methodological challenges for population health research. For example, the calculation of summary measures of population health (SMPH) can be compromised if co-morbidity is not taken into account. One popular co-morbidity adjustment used in SMPH computations relies on a straightforward multiplicative combination of the severity weights for the individual conditions involved. While the convenience and simplicity of the multiplicative model are attractive, its appropriateness has yet to be formally tested. The primary objective of the current study was therefore to examine the empirical evidence in support of this approach. METHODS: The present study drew on information on the prevalence of chronic conditions and a utility-based measure of health-related quality of life (HRQoL), namely the Health Utilities Index Mark 3 (HUI3), available from Cycle 1.1 of the Canadian Community Health Survey (CCHS; 2000–01). Average HUI3 scores were computed for both single and co-morbid conditions, and were also purified by statistically removing the loss of functional health due to health problems other than the chronic conditions reported. The co-morbidity rule was specified as a multiplicative combination of the purified average observed HUI3 utility scores for the individual conditions involved, with the addition of a synergy coefficient s for capturing any interaction between the conditions not explained by the product of their utilities. The fit of the model to the purified average observed utilities for the co-morbid conditions was optimized using ordinary least squares regression to estimate s. Replicability of the results was assessed by applying the method to triple co-morbidities from the CCHS cycle 1.1 database, as well as to double and triple co-morbidities from cycle 2.1 of the CCHS (2003–04). RESULTS: Model fit was optimized at s = .99 (i.e., essentially a straightforward multiplicative model). These results were closely replicated with triple co-morbidities reported on CCHS 2000–01, as well as with double and triple co-morbidities reported on CCHS 2003–04. CONCLUSION: The findings support the simple multiplicative model for computing utilities for co-morbid conditions from the utilities for the individual conditions involved. Future work using a wider variety of conditions and data sources could serve to further evaluate and refine the approach

Dietary nitrate does not have an effect on physical activity outcomes in healthy older adults : a randomized, cross-over trial

Dietary nitrate (〖NO〗_3^-) ingestion appears to enhance exercise capacity and performance in young individuals whereas inconclusive findings have been reported in older people. We conducted a double-blind, cross-over randomized clinical trial in older normal weight and overweight healthy participants testing whether beetroot juice (a rich source of 〖NO〗_3^-) for one week may increase nitric oxide bioavailability via the non-enzymatic pathway and enhance 1) exercise capacity during an incremental exercise test, 2) physical capability and 3) free-living physical activity. Twenty non-smoking healthy participants aged 60-75y and BMI 20.0-29.9kg/m2 were included. Pre and post supplementation resting, sub-maximal, maximal and recovery gas exchanges were measured. Physical capability was measured by hand-grip strength (HGS), time-up-and-go (TUG), repeated-chair-rising-test (RCRT), and 10m walking speed (WLS). Free-living physical activity was assessed by triaxal accelerometry. Changes in urinary and plasma 〖NO〗_3^- concentrations were measured by gas chromatography mass spectrometry. Nineteen participants (M/F=9/10) completed the study. Beetroot juice increased significantly both plasma and urinary 〖NO〗_3^- concentrations (p<0.001) compared to placebo. Beetroot juice did not influence resting, sub-maximal and maximal oxygen consumption during the incremental exercise test. In addition, measures of physical capability and physical activity levels measured in free-living conditions were not modified by beetroot juice ingestion. The positive effects of beetroot juice ingestion on exercise performance seen in young individuals were not replicated in healthy, older adults. Whether aging represents a modifier of the effects of dietary 〖NO〗_3^- on muscular performance is not known and mechanistic studies and larger trials are needed to test this hypothesis. Keywords: inorganic nitrate, nitric oxide, exercise, oxygen consumption, agin

Transcriptomics and proteomics show that selenium affects inflammation, ctoskeleton, and cancer pathways in human rectal biopsies

Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk