Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study

BACKGROUND: Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown. METHODS: In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58–77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis. RESULTS: In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02–5.45], OR0.68[0.59–0.79], respectively;both p<  0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55–0.75], DM OR1.47[1.26–1.72], CKD OR1.61[1.32–1.97], COPD OR1.30[1.07–1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome. CONCLUSIONS: Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities

Water supply of ancient Egyptian settlements: the role of the state. Overview of a relatively equitable scheme from the Old to New Kingdom (ca. 2543-1077 BC).

This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s12685-015-0150-xThe study of the textual and archaeological evidence shows that the water supply of the settlements of ancient Egypt seems to have worked on a simple and a relatively equitable scheme, at least from the Old Kingdom until the New Kingdom (ca. 2543-1077). The water supply of the inhabitants was completely managed by the state, through the local administration which was charged to bring the water, in general from a rural area, into towns and cities and to redistribute it to the inhabitants. The method of supply is illustrated by several sources of evidence, in particular by the well known case of the "water-carriers" of the village of Deir el-Medina. Thus, drawing together text and archaeology, this paper will demonstrate that over an extended period, even when the city was far from a water source, the state did not set up complex installations such as pipe networks or wells to bring water, but preferred a simpler system using the manpower available

Increased Oxidative Burden Associated with Traffic Component of Ambient Particulate Matter at Roadside and Urban Background Schools Sites in London

As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OPAA m−3) and glutathione (OPGSH m−3) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM1.9–10.2. However, when expressed per unit mass of particles OPAA µg−1 showed no significant dependence upon particle size, while OPGSH µg−1 had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.\ud \u

Methods for environment: productivity trade-off analysis in agricultural systems

Trade-off analysis has become an increasingly important approach for evaluating system level outcomes of agricultural production and for prioritising and targeting management interventions in multi-functional agricultural landscapes. We review the strengths and weakness of different techniques available for performing trade-off analysis. These techniques, including mathematical programming and participatory approaches, have developed substantially in recent years aided by mathematical advancement, increased computing power, and emerging insights into systems behaviour. The strengths and weaknesses of the different approaches are identified and discussed, and we make suggestions for a tiered approach for situations with different data availability. This chapter is a modified and extended version of Klapwijk et al. (2014)

The Relationship Between Anthropometric Measures, Blood Gases, and Lung Function in Morbidly Obese White Subjects

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Obesity may cause adverse effects on the respiratory system. The main purpose of this study was to investigate how various measures of obesity are related to arterial blood gases and pulmonary function. Methods This is a cross-sectional study of consecutive morbidly obese patients with normal lung function. Blood gas samples were taken from the radial artery after 5 min of rest with subjects sitting upright. Lung function measurements included dynamic spirometry, static lung volumes, and gas diffusing capacity. Results The 149 patients (77 % women) had a mean (SD) age of 43 years (11 years) and BMI of 45.0 kg/m 2 (6.3 kg/m 2). The mean expiratory reserve volume (ERV) was less than half (49%) of predicted value, whilst most other lung function values were within predicted range. Forty-two patients had an abnormally low pO2 value (&lt;10.7 kPa [80 mmHg]), while eight patients had a high pCO2 value (&gt;6.0 kPa [45 mmHg])

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Study Protocol: insulin and its role in cancer

<p>Abstract</p> <p>Background</p> <p>Studies have shown that metabolic syndrome and its consequent biochemical derangements in the various phases of diabetes may contribute to carcinogenesis. A part of this carcinogenic effect could be attributed to hyperinsulinism. High levels of insulin decrease the production of IGF-1 binding proteins and hence increase levels of free IGF-1. It is well established that bioactivity of free insulin growth factor 1 (IGF-1) increases tumor turnover rate. The objective is to investigate the role of insulin resistance/sensitivity in carcinogenesis by studying the relation between insulin resistance/sensitivity and IGF-1 levels in cancer patients. We postulate that hyperinsulinaemia which prevails during initial phases of insulin resistance (condition prior to overt diabetes) increases bioactivity of free IGF-1, which may contribute to process of carcinogenesis.</p> <p>Methods/Design</p> <p>Based on our pilot study results and power analysis of the same, we have designed a two group case-control study. 800 proven untreated cancer patients (solid epithelial cell tumors) under age of 50 shall be recruited with 200 healthy subjects serving as controls. Insulin resistance/sensitivity and free IGF-1 levels shall be determined in all subjects. Association between the two parameters shall be tested using suitable statistical methods.</p> <p>Discussion</p> <p>Well controlled studies in humans are essential to study the link between insulin resistance, hyperinsulinaemia, IGF-1 and carcinogenesis. This study could provide insights to the role of insulin, insulin resistance, IGF-1 in carcinogenesis although a precise role and the extent of influence cannot be determined. In future, cancer prevention and treatment strategies could revolve around insulin and insulin resistance.</p