Changes in health in England, with analysis by English regions and areas of deprivation, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. METHODS: We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. FINDINGS: Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0-5·8) from 75·9 years (75·9-76·0) to 81·3 years (80·9-81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3-43·6), whereas DALYs were reduced by 23·8% (20·9-27·1), and YLDs by 1·4% (0·1-2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7-41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1-12·7]) and tobacco (10·7% [9·4-12·0]). INTERPRETATION: Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. FUNDING: Bill & Melinda Gates Foundation and Public Health England.

Acute hyperglycemia and oxidative stress: direct cause and effect?

Oxidative stress is increased in Type 2 diabetes and this appears to underlie the development of diabetic complications. Increased oxidative stress is claimed to be triggered directly by acute (sudden-onset) hyperglycemia, but published data do not clearly support a direct cause and effect relationship. In this article, published evidence of a direct prooxidant effect of acute hyperglycemia is presented and discussed in some detail, and conflicts, controversies, and problems are highlighted. Evidence for glucose variability as a possible important trigger of oxidative stress in diabetes is reviewed, with some speculation as to how the field would be advanced if there were more widespread recognition about the role that wide fluctuations in glucose concentration play in diabetic complications. Possible direct or indirect antioxidative effects of various drugs used in the treatment of diabetic subjects are discussed because these may have influenced current understanding of the link between hyperglycemia and oxidative stress. The aims are to reveal the divergence between the available evidence and the accepted view that acute hyperglycemia is a direct trigger of oxidative stress and to suggest areas of research that will help resolve current controversies in this important and challenging area.

Whole blood analysis of phagocytosis, apoptosis, cytokine production, and leukocyte subsets in healthy older men and women: the ZENITH study.

Few studies to date have examined age-related changes in markers of immune status in healthy older individuals. The immune status of 93 healthy individuals aged 55-70 years was assessed by two- and three-color flow cytometry and biochemical analysis. There were significant age effects (p

The clinical effect of dietary supplementation with omega-3 fish oils and/or copper in systemic lupus erythematosus.

OBJECTIVE: To determine the effect of dietary supplementation with omega-3 fish oils with or without copper on disease activity in systemic lupus erythematosus (SLE). Fish oil supplementation has a beneficial effect on murine models of SLE, while exogenous copper can decrease the formation of lupus erythematosus cells in rats with a hydralazine-induced collagen disease. METHODS: A double blind, double placebo controlled factorial trial was performed on 52 patients with SLE. Patients were randomly assigned to 4 treatment groups. Physiological doses of omega-3 fish oils and copper readily obtainable by dietary means were used. One group received 3 g MaxEPA and 3 mg copper, another 3 g MaxEPA and placebo copper, another 3 mg copper and placebo fish oil, and the fourth group received both placebo capsules. Serial measurements of disease activity using the revised Systemic Lupus Activity Measure (SLAM-R) and peripheral blood samples for routine hematological, biochemical, and immunological indices were taken at baseline, 6, 12, and 24 weeks. RESULTS: There was a significant decline in SLAM-R score from 6.12 to 4.69 (p < 0.05) in those subjects taking fish oil compared to placebo. No significant effect on SLAM-R was observed in subjects taking copper. Laboratory variables were unaffected by either intervention. CONCLUSION: In the management of SLE, dietary supplementation with fish oil may be beneficial in modifying symptomatic disease activity.

Zinc supplementation has no effect on lipoprotein metabolism, hemostasis, and putative indices of copper status in healthy men.

Pharmacological doses of zinc can adversely affect body copper status. The resulting copper deficiency can impact directly upon cholesterol metabolism and a suboptimal copper status has been observed to influence markers of hemostasis (specifically fibrinogen and the copper-containing coagulation factors V and VIII). The aim of this investigation was to examine the effect of a low level of zinc supplementation, to include dietary intake, at the United States tolerable upper intake level of 40 mg/d upon indicators of lipid metabolism, hemostasis, and copper. Thirty-eight subjects were recruited onto a double-blind placebo-controlled intervention trial and randomly selected to one of two groups. Group 1 took zinc supplements (30 mg/d) for 14 wk followed by copper supplements (3 mg/d) for 8 wk (to counteract adverse effects, if any, of zinc supplementation). A second group took placebo supplements for the full duration of the trial. Estimated dietary zinc intake approximated 10 mg/d. The effect of supplement was analyzed by repeated-measures analysis of variance (anova). Results indicate that no effect of zinc supplementation on putative indices of copper status, lipoprotein metabolism, and markers of hemostasis. These results indicate that short-term low-level zinc supplementation (total intake 40 mg/d) is not detrimental to health.

Zinc supplementation has no effect on circulating levels of peripheral blood leucocytes and lymphocyte subsets in healthy adult men.

As a result of evidence documenting harmful effects of Zn supplementation on immune function and Cu status, thirty-eight men were recruited onto a Zn supplementation trial. The aim was to examine the effects of chronic Zn supplementation on circulating levels of peripheral blood leucocytes and lymphocyte subsets. Subjects (n 19) took 30 mg Zn/d for 14 weeks followed by 3 mg Cu/d for 8 weeks to counteract adverse effects, if any, of Zn supplementation on immune status resulting from lowered Cu status. A control group (n 19) took placebo supplements for the duration of the trial. Dietary intakes of Zn approximated 10 mg/d. Blood samples, taken throughout the trial, were assessed for full blood profiles and flow cytometric analyses of lymphocyte subsets. Putative indices of Cu status were also examined. Results indicate that there was no effect of Zn supplementation on circulating levels of peripheral blood leucocytes or on lymphocyte subsets. Cu status was also unaltered. Independent of supplement, there appeared to be seasonal variations in selected lymphocyte subsets in both placebo and supplemented groups. Alterations in circulating levels of B cells (cluster of differentiation (CD) 19), memory T cells (CD45RO) and expression of the intracellular adhesion molecule-1 (CD54) on T cells were observed. Findings indicated no adverse effects of Zn supplementation on immune status or Cu status and support the US upper level of Zn tolerance of 40 mg/d. The seasonal variations observed in lymphocyte subsets in the group as a whole could have implications for seasonal variability in the incidence of infectious diseases.

The immune system as a physiological indicator of marginal copper status?

Cu appears to have many important functional roles in the body that apparently relate, among others, to the maintenance of immune function, bone health and haemostasis. Some have suggested a role for long-term marginal Cu deficiency in the aetiology of a number of degenerative diseases. Accurate diagnosis of marginal Cu deficiency, however, has remained elusive despite an increased understanding of the biochemistry of Cu and its physiological roles in the body. Traditional markers of Cu status, such as serum Cu and caeruloplasmin protein concentrations are insensitive to subtle changes in Cu status. Cu-containing enzymes, such as Cu-Zn-superoxide dismutase, cytochrome c oxidase and diamine oxidase, may be more reliable but evidence to date is not conclusive. Development of markers sensitive to marginal Cu status is essential before conclusions can be drawn concerning the risks of long-term intake of suboptimal dietary Cu. As Cu appears to be essential for maintenance of immune function, activities of specific immunological markers, altered in Cu deficiency, offer alternatives. This review evaluates a selection of immunological markers that could be considered potentially sensitive markers of marginal Cu status. The indices of immune function reviewed are neutrophil function, interleukin 2 production, blastogenic response to mitogens and lymphocyte subset phenotyping.