Validation and recalibration of the Framingham cardiovascular disease risk models in an Australian Indigenous cohort: Does the current Framingham risk calculator accurately estimate true CVD risk for Indigenous Australians?

In this study, we validated both the 1991 and 2008 Framingham CVD models using a cohort of Aboriginal and Torres Strait Islander adults drawn from remote Indigenous communities in Far North Queensland. Recalibration was also conducted to help generate more accurate CVD risk predictions for this population. Finally, we developed a CVD risk chart that could help improve the assessment and management of CVD in the Australian Indigenous population, particularly those in remote regions of Australia.The research reported in this paper is a project of the Australian Primary Health Care Research Institute, which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research, Evaluation and Development Strategy

Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses.

BACKGROUND: Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. METHODS AND FINDINGS: A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. CONCLUSIONS: Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.US NIH (Grant ID: R37CA070867), Ingram Professorship, Anne Potter Wilson , National Institutes of Health (Grant IDs: R25CA160056-03, U19CA148065, U19CA148107, U19CA148127, U19CA148537, Cancer Research UK, Prostate Cancer UK, The Institute of Cancer Research, Royal Marsden Biomedical Research Centre, National Institute of Health Research (Grant ID: C5047/A17528)This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/10.1371/journal.pmed.100211

Investigating the genetic relationship between Alzheimer's disease and cancer using GWAS summary statistics.

Growing evidence from both epidemiology and basic science suggest an inverse association between Alzheimer's disease (AD) and cancer. We examined the genetic relationship between AD and various cancer types using GWAS summary statistics from the IGAP and GAME-ON consortia. Sample size ranged from 9931 to 54,162; SNPs were imputed to the 1000 Genomes European panel. Our results based on cross-trait LD Score regression showed a significant positive genetic correlation between AD and five cancers combined (colon, breast, prostate, ovarian, lung; r g = 0.17, P = 0.04), and specifically with breast cancer (ER-negative and overall; r g = 0.21 and 0.18, P = 0.035 and 0.034) and lung cancer (adenocarcinoma, squamous cell carcinoma and overall; r g = 0.31, 0.38 and 0.30, P = 0.029, 0.016, and 0.006). Estimating the genetic correlation in specific functional categories revealed mixed positive and negative signals, notably stronger at annotations associated with increased enhancer activity. This suggests a role of gene expression regulators in the shared genetic etiology between AD and cancer, and that some shared variants modulate disease risk concordantly while others have effects in opposite directions. Due to power issues, we did not detect cross-phenotype associations at individual SNPs. This genetic overlap is not likely driven by a handful of major loci. Our study is the first to examine the co-heritability of AD and cancer leveraging large-scale GWAS results. The functional categories highlighted in this study need further investigation to illustrate the details of the genetic sharing and to bridge between different levels of associations

Improving the physical health of people with severe mental illness in a low secure forensic unit: An uncontrolled evaluation study of staff training and physical health care plans

The life expectancy of people with severe mental illnesses is substantially reduced, and monitoring and screening for physical health problems is a key part of addressing this health inequality. Inpatient admission presents a window of opportunity for this health-care activity. The present study was conducted in a forensic mental health unit in England. A personal physical health plan incorporating clearly-presented and easily-understood values and targets for health status in different domains was developed. Alongside this, a brief physical education session was delivered to health-care staff (n = 63). Printed learning materials and pedometers and paper tape measures were also provided. The impact was evaluated by a single-group pretest post-test design; follow-up measures were 4 months' post-intervention. The feasibility and acceptability of personal health plans and associated resources were examined by free-text questionnaire responses. Fifty-seven staff provided measures of attitudes and knowledge before training and implementation of the physical health plans. Matched-pairs analysis indicated a modest but statistically-significant improvement in staff knowledge scores and attitudes to involvement in physical health care. Qualitative feedback indicated limited uptake of the care plans and perceived need for additional support for better adoption of this initiative. Inpatient admission is a key setting for assessing physical health and promoting improved management of health problems. Staff training and purpose-designed personalized care plans hold potential to improve practice and outcomes in this area, but further support for such innovations appears necessary for their uptake in inpatient mental health settings

Functional variants in DCAF4 associated with lung cancer risk in European populations.

Cullin-RING ubiquitin ligases (CRLs) responsible for substrate specificity of ubiquitination play a key role in cell-cycle control and DNA damage response. In this study, we assessed associations between 16 599 SNPs in 115 CRL genes and lung cancer risk by using summary data of six published genome-wide association studies (GWASs) of 12 160 cases and 16 838 cases of European ancestry. As a result, we identified three independent SNPs in DCAF4 (rs117781739, rs12587742 and rs2240980) associated with lung cancer risk (odds ratio = 0.91, 1.09 and 1.09, respectively; 95% confidence interval = 0.88-0.95, 1.05-1.14 and 1.05-1.13, respectively; and P = 3.99 × 10-6, 4.97 × 10-5 and 1.44 × 10-5, respectively) after multiple comparison correction by a false discovery rate <0.05. Since SNP rs12587742 is located within the promoter region and one CpG island of DCAF4, we further performed in silico functional analyses and found that the rs12587742 variant A allele was associated with an increased mRNA expression (P = 2.20 × 10-16, 1.79 × 10-13 and 0.001 in blood cells, normal lung tissues and tumor tissues of lung squamous carcinoma, respectively) and a decreased methylation status (P = 2.48 × 10-9 and 0.032 in adipose and lung tumor tissues, respectively). Moreover, evidence from differential expression analyses further supported an oncogenic effect of DCAF4 on lung cancer, with higher mRNA levels in both lung squamous carcinoma and adenocarcinoma (P = 4.48 × 10-11 and 1.22 × 10-9, respectively) than in adjacent normal tissues. Taken together, our results suggest that rs12587742 is associated with an increased lung cancer risk, possibly by up-regulating mRNA expression and decreasing methylation status of DCAF4

What are the barriers to the diagnosis and management of chronic respiratory disease in sub-Saharan Africa? A qualitative study with healthcare workers, national and regional policy stakeholders in five countries

Objectives Chronic respiratory diseases (CRD) are among the top four non-communicable diseases globally. They are associated with poor health and approximately 4 million deaths every year. The rising burden of CRD in low/middle-income countries will strain already weak health systems. This study aimed to explore the perspectives of healthcare workers and other health policy stakeholders on the barriers to effective diagnosis and management of CRD in Kenya, Malawi, Sudan, Tanzania and Uganda. Study design Qualitative descriptive study. Settings Primary, secondary and tertiary health facilities, government agencies and civil society organisations in five sub-Saharan African countries. Participants We purposively selected 60 national and district-level policy stakeholders, and 49 healthcare workers, based on their roles in policy decision-making or health provision, and conducted key informant interviews and in-depth interviews, respectively, between 2018 and 2019. Data were analysed through framework approach. Results We identified intersecting vicious cycles of neglect of CRD at strategic policy and healthcare facility levels. Lack of reliable data on burden of disease, due to weak information systems and diagnostic capacity, negatively affected inclusion in policy; this, in turn, was reflected by low budgetary allocations for diagnostic equipment, training and medicines. At the healthcare facility level, inadequate budgetary allocations constrained diagnostic capacity, quality of service delivery and collection of appropriate data, compounding the lack of routine data on burden of disease. Conclusion Health systems in the five countries are ill-equipped to respond to CRD, an issue that has been brought into sharp focus as countries plan for post-COVID-19 lung diseases. CRD are underdiagnosed, under-reported and underfunded, leading to a vicious cycle of invisibility and neglect. Appropriate diagnosis and management require health systems strengthening, particularly at the primary healthcare level

Vitamin C in plasma is inversely related to blood pressure and change in blood pressure during the previous year in young Black and White women

BackgroundThe prevalence of hypertension and its contribution to cardiovascular disease risk makes it imperative to identify factors that may help prevent this disorder. Extensive biological and biochemical data suggest that plasma ascorbic acid may be such a factor. In this study we examined the association between plasma ascorbic acid concentration and blood pressure (BP) in young-adult women.MethodsParticipants were 242 Black and White women aged 18-21 yr from the Richmond, CA, cohort of the National Heart, Lung and Blood Institute Growth and Health Study. We examined the associations of plasma ascorbic acid with BP at follow-up year 10, and with change in BP during the previous year.ResultsIn cross-sectional analysis, plasma ascorbic acid at year 10 was inversely associated with systolic BP and diastolic BP after adjusting for race, body mass index, education, and dietary intake of fat and sodium. Persons in the highest one-fourth of the plasma ascorbic acid distribution had 4.66 mmHg lower systolic BP (95% CI 1.10 to 8.22 mmHg, p = 0.005) and 6.04 mmHg lower diastolic BP (95% CI 2.70 to 9.38 mmHg, p = 0.0002) than those in the lowest one-fourth of the distribution. In analysis of the change in BP, plasma ascorbic acid was also inversely associated with change in systolic BP and diastolic BP during the previous year. While diastolic blood pressure among persons in the lowest quartile of plasma ascorbic acid increased by 5.97 mmHg (95% CI 3.82 to 8.13 mmHg) from year 9 to year 10, those in the highest quartile of plasma vitamin C increased by only 0.23 mmHg (95% CI -1.90 to +2.36 mmHg) (test for linear trend: p &lt; 0.0001). A similar effect was seen for change in systolic BP, p = 0.005.ConclusionPlasma ascorbic acid was found to be inversely associated with BP and change in BP during the prior year. The findings suggest the possibility that vitamin C may influence BP in healthy young adults. Since lower BP in young adulthood may lead to lower BP and decreased incidence of age-associated vascular events in older adults, further investigation of treatment effects of vitamin C on BP regulation in young adults is warranted