National Diet and Nutrition Survey Rolling programme Years 9 to 11 (2016/2017 to 2018/2019) - A survey carried out on behalf of Public Health England and the Food Standards Agency

The National Diet and Nutrition Survey Rolling Programme (NDNS RP) is a continuous crosssectional survey, designed to assess the diet, nutrient intake and nutritional status of the general population aged 1.5 years and over living in private households in the UK. A representative sample of around 1,000 people (500 adults and 500 children) take part in the NDNS RP each year. Fieldwork for Years 9 to 11 of the NDNS RP was carried out between April 2016 and June 2019. The survey comprised an interview, a 4-day estimated diet diary, physical measurements and a blood and urine sample. Results are used by government to monitor progress toward diet and nutrition objectives of UK Health Departments and to develop policy interventions. The foods, nutrients and blood and urine measures presented in this report were selected for their nutritional and public health relevance to current dietary concerns in the UK. Results are analysed for 7 age groups: 1.5 to 3 years; 4 to 10 years; 11 to 18 years; 19 to 64 years; 65 years and over; 65 to 74 years and 75 years and over, split by sex in all except the youngest age group. The report includes: • descriptive statistics of food consumption, nutrient intake and nutritional status including proportion of the population meeting government recommendations for NDNS RP Years 9 to 11 (2016/17 to 2018/19) and comparison with results from years 7&8 (2014/15 to 2015/16). • trends over time in relation to food consumption, nutrient intakes and nutritional status in the UK for the first 11 years of the NDNS RP (2008/09 to 2018/19)PHE and Food Standards Agenc

Clinical peripherality: development of a peripherality index for rural health services

BACKGROUND: The configuration of rural health services is influenced by geography. Rural health practitioners provide a broader range of services to smaller populations scattered over wider areas or more difficult terrain than their urban counterparts. This has implications for training and quality assurance of outcomes. This exploratory study describes the development of a "clinical peripherality" indicator that has potential application to remote and rural general practice communities for planning and research purposes. METHODS: Profiles of general practice communities in Scotland were created from a variety of public data sources. Four candidate variables were chosen that described demographic and geographic characteristics of each practice: population density, number of patients on the practice list, travel time to nearest specialist led hospital and travel time to Health Board administrative headquarters. A clinical peripherality index, based on these variables, was derived using factor analysis. Relationships between the clinical peripherality index and services offered by the practices and the staff profile of the practices were explored in a series of univariate analyses. RESULTS: Factor analysis on the four candidate variables yielded a robust one-factor solution explaining 75% variance with factor loadings ranging from 0.83 to 0.89. Rural and remote areas had higher median values and a greater scatter of clinical peripherality indices among their practices than an urban comparison area. The range of services offered and the profile of staffing of practices was associated with the peripherality index. CONCLUSION: Clinical peripherality is determined by the nature of the practice and its location relative to secondary care and administrative and educational facilities. It has features of both gravity model-based and travel time/accessibility indicators and has the potential to be applied to training of staff for rural and remote locations and to other aspects of health policy and planning. It may assist planners in conceptualising the effects on general practices of centralising specialist clinical services or administrative and educational facilities

Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission

Immune-mediated inflammatory diseases (IMIDs) are typically characterised by relapsing and remitting flares of inflammation. However, the unpredictability of disease flares impedes their study. Addressing this critical knowledge gap, we use the experimental medicine approach of immunomodulatory drug withdrawal in rheumatoid arthritis (RA) remission to synchronise flare processes allowing detailed characterisation. Exploratory mass cytometry analyses reveal three circulating cellular subsets heralding the onset of arthritis flare – CD45RO+PD1hi CD4+ and CD8+ T cells, and CD27+CD86+CD21- B cells – further characterised by single-cell sequencing. Distinct lymphocyte subsets including cytotoxic and exhausted CD4+ memory T cells, memory CD8+CXCR5+ T cells, and IGHA1+ plasma cells are primed for activation in flare patients. Regulatory memory CD4+ T cells (Treg cells) increase at flare onset, but with dysfunctional regulatory marker expression compared to drug-free remission. Significant clonal expansion is observed in T cells, but not B cells, after drug cessation; this is widespread throughout memory CD8+ T cell subsets but limited to the granzyme-expressing cytotoxic subset within CD4+ memory T cells. Based on our observations, we suggest a model of immune dysregulation for understanding RA flare, with potential for further translational research towards novel avenues for its treatment and prevention

Impact of nonoptimal intakes of saturated, polyunsaturated, and trans fat on global burdens of coronary heart disease

Background: Saturated fat (SFA), ω‐6 (n‐6) polyunsaturated fat (PUFA), and trans fat (TFA) influence risk of coronary heart disease (CHD), but attributable CHD mortalities by country, age, sex, and time are unclear. Methods and Results: National intakes of SFA, n‐6 PUFA, and TFA were estimated using a Bayesian hierarchical model based on country‐specific dietary surveys; food availability data; and, for TFA, industry reports on fats/oils and packaged foods. Etiologic effects of dietary fats on CHD mortality were derived from meta‐analyses of prospective cohorts and CHD mortality rates from the 2010 Global Burden of Diseases study. Absolute and proportional attributable CHD mortality were computed using a comparative risk assessment framework. In 2010, nonoptimal intakes of n‐6 PUFA, SFA, and TFA were estimated to result in 711 800 (95% uncertainty interval [UI] 680 700–745 000), 250 900 (95% UI 236 900–265 800), and 537 200 (95% UI 517 600–557 000) CHD deaths per year worldwide, accounting for 10.3% (95% UI 9.9%–10.6%), 3.6%, (95% UI 3.5%–3.6%) and 7.7% (95% UI 7.6%–7.9%) of global CHD mortality. Tropical oil–consuming countries were estimated to have the highest proportional n‐6 PUFA– and SFA‐attributable CHD mortality, whereas Egypt, Pakistan, and Canada were estimated to have the highest proportional TFA‐attributable CHD mortality. From 1990 to 2010 globally, the estimated proportional CHD mortality decreased by 9% for insufficient n‐6 PUFA and by 21% for higher SFA, whereas it increased by 4% for higher TFA, with the latter driven by increases in low‐ and middle‐income countries. Conclusions: Nonoptimal intakes of n‐6 PUFA, TFA, and SFA each contribute to significant estimated CHD mortality, with important heterogeneity across countries that informs nation‐specific clinical, public health, and policy priorities.peer-reviewe

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8–14.4 million) incident T2D cases, representing 70.3% (68.8–71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0–27.1%)), excess refined rice and wheat intake (24.6% (22.3–27.2%)) and excess processed meat intake (20.3% (18.3–23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4–87.7%)) and Latin America and the Caribbean (81.8% (80.1–83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1–60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.publishedVersio

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms