Catalog of 199 register-based definitions of chronic conditions

Introduction: The aim of the current study was to present and discuss a broad range of register-based definitions of chronic conditions for use in register research, as well as the challenges and pitfalls when defining chronic conditions by the use of registers. Materials and methods: The definitions were defined based on information from nationwide Danish public healthcare registers. Medical and epidemiological specialists identified and grouped relevant diagnosis codes that covered chronic conditions, using the International Classification System version 10 (ICD-10). Where relevant, prescription and other healthcare data were also used to define the chronic conditions. Results: We identified 199 chronic conditions and subgroups, which were divided into four groups according to a medical judgment of the expected duration of the conditions, as follows. Category I: Stationary to progressive conditions (maximum register inclusion time of diagnosis since the start of the register in 1994). Category II: Stationary to diminishing conditions (10 years of register inclusion after time of diagnosis). Category III: Diminishing conditions (5 years of register inclusion after time of diagnosis). Category IV: Borderline conditions (2 years of register inclusion time following diagnosis). The conditions were primarily defined using hospital discharge diagnoses; however, for 35 conditions, including common conditions such as diabetes, chronic obstructive lung disease and allergy, more complex definitions were proposed based on record linkage between multiple registers, including registers of prescribed drugs and use of general practitioners’ services. Conclusions: This study provided a catalog of register-based definitions for chronic conditions for use in healthcare planning and research, which is, to the authors’ knowledge, the largest currently compiled in a single study

Is Cancer survival associated with cancer symptom awareness and barriers to seeking medical help in England? An ecological study

Abstract BACKGROUND: Campaigns aimed at raising cancer awareness and encouraging early presentation have been implemented in England. However, little is known about whether people with low cancer awareness and increased barriers to seeking medical help have worse cancer survival, and whether there is a geographical variation in cancer awareness and barriers in England. METHODS: From population-based surveys (n=35?308), using the Cancer Research UK Cancer Awareness Measure, we calculated the age- and sex-standardised symptom awareness and barriers scores for 52 primary care trusts (PCTs). These measures were evaluated in relation to the sex-, age-, and type of cancer-standardised cancer survival index of the corresponding PCT, from the National Cancer Registry, using linear regression. Breast, lung, and bowel cancer survival were analysed separately. RESULTS: Cancer symptom awareness and barriers scores varied greatly between geographical regions in England, with the worst scores observed in socioeconomically deprived parts of East London. Low cancer awareness score was associated with poor cancer survival at PCT level (estimated slope=1.56, 95% CI: 0.56; 2.57). The barriers score was not associated with overall cancer survival, but it was associated with breast cancer survival (estimated slope=-0.66, 95% CI: -1.20; -0.11). Specific barriers, such as embarrassment and difficulties in arranging transport to the doctor's surgery, were associated with worse breast cancer survival. CONCLUSIONS: Cancer symptom awareness and cancer survival are associated. Campaigns should focus on improving awareness about cancer symptoms, especially in socioeconomically deprived areas. Efforts should be made to alleviate barriers to seeking medical help in women with symptoms of breast cancer.British Journal of Cancer advance online publication 18 August 2016; doi:10.1038/bjc.2016.246 www.bjcancer.com

Urine/Plasma Neutrophil Gelatinase Associated Lipocalin Ratio Is a Sensitive and Specific Marker of Subclinical Acute Kidney Injury in Mice

Background Detection of acute kidney injury (AKI) is still a challenge if conventional markers of kidney function are within reference range. We studied the sensitivity and specificity of NGAL as an AKI marker at different degrees of renal ischemia. Methods Male C57BL/6J mice were subjected to 10-, 20- or 30-min unilateral renal ischemia, to control operation or no operation, and AKI was evaluated 1 day later by histology, immunohistochemistry, BUN, creatinine, NGAL (plasma and urine) and renal NGAL mRNA expression. Results A short (10-min) ischemia did not alter BUN or kidney histology, but elevated plasma and urinary NGAL level and renal NGAL mRNA expression although to a much smaller extent than longer ischemia. Surprisingly, control operation elevated plasma NGAL and renal NGAL mRNA expression to a similar extent as 10-min ischemia. Further, the ratio of urine to plasma NGAL was the best parameter to differentiate a 10-min ischemic injury from control operation, while it was similar in the non and control-operated groups. Conclusions These results suggest that urinary NGAL excretion and especially ratio of urine to plasma NGAL are sensitive and specific markers of subclinical acute kidney injury in mice

Plasma neutrophil gelatinase associated lipocalin (NGAL) is associated with kidney function in uraemic patients before and after kidney transplantation

<p>Abstract</p> <p>Background</p> <p>Neutrophil gelatinase associated lipocalin (NGAL) is a biomarker of kidney injury. We examined plasma levels of NGAL in a cohort of 57 kidney allograft recipients (Tx group, 39 ± 13 years), a uraemic group of 40 patients remaining on the waiting list (47 ± 11 years) and a control group of 14 healthy subjects matched for age, sex and body mass index (BMI). The kidney graft recipients were studied at baseline before transplantation and 3 and 12 months after transplantation and the uraemic group at baseline and after 12 months.</p> <p>Methods</p> <p>NGAL was measured using a validated in-house Time-Resolved Immuno-flourometric assay (TRIFMA). Repeated measurements differed by < 10% and mean values were used for statistical analyses. Spearman rank order correlation analysis and the Kruskal-Wallis non-parametric test were used to evaluate the association of NGAL concentrations with clinical parameters.</p> <p>Results</p> <p>Plasma NGAL levels before transplantation in the Tx and uraemic groups were significantly higher than in the healthy controls (1,251 μg/L, 1,478 μg/L vs. 163 μg/L, p < 0.0001). In the Tx group NGAL concentrations were associated with serum creatinine (R = 0.51, p < 0.0001), duration of end-stage renal failure (R = 0.41, p = 0.002) and leukocyte count (R = 0.29, p < 0.026). At 3 and 12 months plasma NGAL concentrations declined to 223 μg/L and 243 μg/L, respectively and were associated with homocysteine (R = 0.39, p = 0.0051 and R = 0.47, p = 0.0007).</p> <p>Conclusions</p> <p>Plasma NGAL is a novel marker of kidney function, which correlates to duration of end-stage renal failure (ESRD) and serum creatinine in uraemic patients awaiting kidney transplantation. Plasma NGAL is associated with homocysteine in transplanted patients. The prognostic value of these findings requires further studies.</p

Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.

Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health

Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.

Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health

Shells and humans: molluscs and other coastal resources from the earliest human occupations at the Mesolithic shell midden of El Mazo (Asturias, Northern Spain)

Human populations exploited coastal areas with intensity during the Mesolithic in Atlantic Europe, resulting in the accumulation of large shell middens. Northern Spain is one of the most prolific regions, and especially the so-called Asturian area. Large accumulations of shellfish led some scholars to propose the existence of intensification in the exploitation of coastal resources in the region during the Mesolithic. In this paper, shell remains (molluscs, crustaceans and echinoderms) from stratigraphic units 114 and 115 (dated to the early Mesolithic c. 9 kys cal BP) at El Mazo cave (Asturias, northern Spain) were studied in order to establish resource exploitation patterns and environmental conditions. Species representation showed that limpets, top shells and sea urchins were preferentially exploited. One-millimetre mesh screens were crucial in establishing an accurate minimum number of individuals for sea urchins and to determine their importance in exploitation patterns. Environmental conditions deduced from shell assemblages indicated that temperate conditions prevailed at the time of the occupation and the morphology of the coastline was similar to today (rocky exposed shores). Information recovered relating to species representation, collection areas and shell biometry reflected some evidence of intensification (reduced shell size, collection in lower areas of exposed shores, no size selection in some units and species) in the exploitation of coastal resources through time. However, the results suggested the existence of changes in collection strategies and resource management, and periods of intense shell collection may have alternated with times of shell stock recovery throughout the Mesolithic.This research was performed as part of the project “The human response to the global climatic change in a littoral zone: the case of the transition to the Holocene in the Cantabrian coast (10,000–5000 cal BC) (HAR2010-22115-C02-01)” funded by the Spanish Ministry of Economy and Competitiveness. AGE was funded by the University of Cantabria through a predoctoral grant and IGZ was funded by the Spanish Ministry of Economy and Competitiveness through a Juan de la Cierva grant. We also would like to thank the University of Cantabria and the IIIPC for providing support, David Cuenca-Solana, Alejandro García Moreno and Lucia Agudo Pérez for their help. We also thank Jennifer Jones for correcting the English. Comments from two anonymous reviewers helped to improve the paper

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference