Identifying extreme COVID-19 mortality risks in English small areas: a disease cluster approach

The COVID-19 pandemic is having a huge impact worldwide and has highlighted the extent of health inequalities between countries but also in small areas within a country. Identifying areas with high mortality is important both of public health mitigation in COVID-19 outbreaks, and of longer term efforts to tackle social inequalities in health. In this paper we consider different statistical models and an extension of a recent method to analyze COVID-19 related mortality in English small areas during the first wave of the epidemic in the first half of 2020. We seek to identify hotspots, and where they are most geographically concentrated, taking account of observed area factors as well as spatial correlation and clustering in regression residuals, while also allowing for spatial discontinuities. Results show an excess of COVID-19 mortality cases in small areas surrounding London and in other small areas in North-East and and North-West of England. Models alleviating spatial confounding show ethnic isolation, air quality and area morbidity covariates having a significant and broadly similar impact on COVID-19 mortality, whereas nursing home location seems to be slightly less important.This work has been supported by Projects MTM2017-82553-R (AEI/FEDER, UE) and Project PID2020-113125RB-I00/MCIN/AEI/10.13039/501100011033). Funding Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature

The MUSE view of the host galaxy of GRB 100316D

The low distance, $z=0.0591$, of GRB 100316D and its association with SN 2010bh represent two important motivations for studying this host galaxy and the GRB's immediate environment with the Integral-Field Spectrographs like VLT/MUSE. Its large field-of-view allows us to create 2D maps of gas metallicity, ionization level, and the star-formation rate distribution maps, as well as to investigate the presence of possible host companions. The host is a late-type dwarf irregular galaxy with multiple star-forming regions and an extended central region with signatures of on-going shock interactions. The GRB site is characterized by the lowest metallicity, the highest star-formation rate and the youngest ($\sim$ 20-30 Myr) stellar population in the galaxy, which suggest a GRB progenitor stellar population with masses up to 20 -- 40 $M_{\odot}$. We note that the GRB site has an offset of $\sim$660pc from the most luminous SF region in the host. The observed SF activity in this galaxy may have been triggered by a relatively recent gravitational encounter between the host and a small undetected ($L_{H\alpha} \leq 10^{36}$ erg/s) companion

Recommendations for physical activity and exercise in persons living with Systemic Lupus Erythematosus (SLE): consensus by an international task force

Objective: This international task force aimed to provide healthcare professionals and persons living with systemic lupus erythematosus (SLE) with consensus-based recommendations for physical activity and exercise in SLE. Methods: Based on evidence from a systematic literature review and expert opinion, 3 overarching principles and 15 recommendations were agreed on by Delphi consensus. Results: The overarching principles highlight the importance of shared decision-making and the need to explain the benefits of physical activity to persons living with SLE and other healthcare providers. The 15 specific recommendations state that physical activity is generally recommended for all people with SLE, but in some instances, a medical evaluation may be needed to rule out contraindications. Pertaining to outdoor activity, photoprotection is necessary. Both aerobic and resistance training programmes are recommended, with a gradual increase in frequency and intensity, which should be adapted for each individual, and ideally supervised by qualified professionals. Conclusion: In summary, the consensus reached by the international task force provides a valuable framework for the integration of physical activity and exercise into the management of SLE, offering a tailored evidence-based and eminence-based approach to enhance the well-being of individuals living with this challenging autoimmune condition

Impact of previous sepsis on the accuracy of procalcitonin for the early diagnosis of blood stream infection in critically ill patients

<p>Abstract</p> <p>Background</p> <p>Blood stream infections (BSI) are life-threatening infections in intensive care units (ICU), and prognosis is highly dependent on early detection. Procalcitonin levels have been shown to accurately and quickly distinguish between BSI and noninfectious inflammatory states in critically ill patients. It is, however, unknown to what extent a recent history of sepsis (namely, secondary sepsis) can affect diagnosis of BSI using PCT.</p> <p>Methods</p> <p>review of the medical records of every patient with BSI in whom PCT dosage at the onset of sepsis was available between 1^stSeptember, 2006 and 31^stJuly, 2007.</p> <p>Results</p> <p>179 episodes of either primary (<it>n </it>= 117) or secondary (<it>n </it>= 62) sepsis were included. Procalcitonin levels were found to be markedly lower in patients with secondary sepsis than in those without (6.4 [9.5] vs. 55.6 [99.0] ng/mL, respectively; <it>p </it>< 0.001), whereas the SOFA score was similar in the two groups. Although patients in the former group were more likely to have received steroids and effective antibiotic therapy prior to the BSI episode, and despite a higher proportion of candidemia in this group, a low PCT value was found to be independently associated with secondary sepsis (Odd Ratio = 0.33, 95% Confidence Interval: 0.16–0.70; <it>p </it>= 0.004). Additional patients with suspected but unconfirmed sepsis were used as controls (<it>n </it>= 23). Thus, diagnostic accuracy of PCT as assessed by the area under the receiver-operating characteristic curves (AUROCC) measurement was decreased in the patients with secondary sepsis compared to those without (AUROCC = 0.805, 95% CI: 0.699–0.879, vs. 0.934, 95% CI: 0.881–0.970, respectively; <it>p </it>< 0.050).</p> <p>Conclusion</p> <p>In a critically ill patient with BSI, PCT elevation and diagnosis accuracy could be lower if sepsis is secondary than in those with a first episode of infection.</p

Shared component modelling as an alternative to assess geographical variations in medical practice: gender inequalities in hospital admissions for chronic diseases

<p>Abstract</p> <p>Background</p> <p>Small area analysis is the most prevalent methodological approach in the study of unwarranted and systematic variation in medical practice at geographical level. Several of its limitations drive researchers to use disease mapping methods -deemed as a valuable alternative. This work aims at exploring these techniques using - as a case of study- the gender differences in rates of hospitalization in elderly patients with chronic diseases.</p> <p>Methods</p> <p>Design and study setting: An empirical study of 538,358 hospitalizations affecting individuals aged over 75, who were admitted due to a chronic condition in 2006, were used to compare Small Area Analysis (SAVA), the Besag-York-Mollie (BYM) modelling and the Shared Component Modelling (SCM). Main endpoint: Gender spatial variation was measured, as follows: SAVA estimated gender-specific utilization ratio; BYM estimated the fraction of variance attributable to spatial correlation in each gender; and, SCM estimated the fraction of variance shared by the two genders, and those specific for each one.</p> <p>Results</p> <p>Hospitalization rates due to chronic diseases in the elderly were higher in men (median per area 21.4 per 100 inhabitants, interquartile range: 17.6 to 25.0) than in women (median per area 13.7 per 100, interquartile range: 10.8 to 16.6). Whereas Utilization Ratios showed a similar geographical pattern of variation in both genders, BYM found a high fraction of variation attributable to spatial correlation in both men (71%, CI95%: 50 to 94) and women (62%, CI95%: 45 to 77). In turn, SCM showed that the geographical admission pattern was mainly shared, with just 6% (CI95%: 4 to 8) of variation specific to the women component.</p> <p>Conclusions</p> <p>Whereas SAVA and BYM focused on the magnitude of variation and on allocating where variability cannot be due to chance, SCM signalled discrepant areas where latent factors would differently affect men and women.</p

Analysis of latent tuberculosis and mycobacterium avium infection data using mixture models

BACKGROUND: Estimation of the frequency of latent tuberculosis infection (LTBI) is difficult in areas with low tuberculosis infection rates and high exposure to non-tuberculous mycobacteria (NTM), including BCG vaccination. The objective was to assess LTBI and M avium infection and to estimate their probability based on skin tests responses in an infant population from a region with the aforementioned characteristics. METHODS: A population-based tuberculin skin test (TST) and sensitin (M avium) survey was conducted on seven years old infants in Biscay, a province from The Basque Country (Spain). 2268 schoolchildren received sensitin and 5277 TST. Participation rate was 89%. Commonly used estimation methods were compared with a method based on the fit of mixture models using the Expectation Maximization algorithm. Functions estimating the probabilities of LTBI and M avium infection given the observed skin tests responses were developed for vaccinated and unvaccinated children. RESULTS: LTBI prevalences varied widely according to the estimation method. The mixture model provided prevalences higher than expected although intermediates between those obtained by currently recommended approaches. Exposure to previous BCG vaccine produces an upward shift of an average of about 3 mm on the induration size to attain the same probability of infection. CONCLUSION: Our results confirm the commonplace exposure to NTM which effect should be taken into account when performing and assessing tuberculin surveys. The use of mixture analysis under the empirical Bayes framework allows to better estimate the probability of LTBI in settings with presence of other NTM and high BCG-vaccination coverage. An estimation of the average effect of BCG vaccination on TST induration is also provided. These models maximise information coming from classical tuberculin surveys and could be used together with the newly developed blood tests to improve survey's specificity and cost-effectiveness

Comprehensive in vitro and in vivo studies of novel melt-derived Nb-substituted 45S5 bioglass reveal its enhanced bioactive properties for bone healing

The present work presents and discusses the results of a comprehensive study on the bioactive properties of Nb-substituted silicate glass derived from 45S5 bioglass. In vitro and in vivo experiments were performed. We undertook three different types of in vitro analyses: (i) investigation of the kinetics of chemical reactivity and the bioactivity of Nb-substituted glass in simulated body fluid (SBF) by 31P MASNMR spectroscopy, (ii) determination of ionic leaching profiles in buffered solution by inductively coupled plasma optical emission spectrometry (ICP-OES), and (iii) assessment of the compatibility and osteogenic differentiation of human embryonic stem cells (hESCs) treated with dissolution products of different compositions of Nb-substituted glass. The results revealed that Nb-substituted glass is not toxic to hESCs. Moreover, adding up to 1.3 mol% of Nb2O5 to 45S5 bioglass significantly enhanced its osteogenic capacity. For the in vivo experiments, trial glass rods were implanted into circular defects in rat tibia in order to evaluate their biocompatibility and bioactivity. Results showed all Nb-containing glass was biocompatible and that the addition of 1.3 mol% of Nb2O5, replacing phosphorous, increases the osteostimulation of bioglass. Therefore, these results support the assertion that Nb-substituted glass is suitable for biomedical applications

Low Concentrations of Methamphetamine Can Protect Dopaminergic Cells against a Larger Oxidative Stress Injury: Mechanistic Study

Mild stress can protect against a larger insult, a phenomenon termed preconditioning or tolerance. To determine if a low intensity stressor could also protect cells against intense oxidative stress in a model of dopamine deficiency associated with Parkinson disease, we used methamphetamine to provide a mild, preconditioning stress, 6-hydroxydopamine (6-OHDA) as a source of potentially toxic oxidative stress, and MN9D cells as a model of dopamine neurons. We observed that prior exposure to subtoxic concentrations of methamphetamine protected these cells against 6-OHDA toxicity, whereas higher concentrations of methamphetamine exacerbated it. The protection by methamphetamine was accompanied by decreased uptake of both [3H] dopamine and 6-OHDA into the cells, which may have accounted for some of the apparent protection. However, a number of other effects of methamphetamine exposure suggest that the drug also affected basic cellular survival mechanisms. First, although methamphetamine preconditioning decreased basal pERK1/2 and pAkt levels, it enhanced the 6-OHDA-induced increase in these phosphokinases. Second, the apparent increase in pERK1/2 activity was accompanied by increased pMEK1/2 levels and decreased activity of protein phosphatase 2. Third, methamphetamine upregulated the pro-survival protein Bcl-2. Our results suggest that exposure to low concentrations of methamphetamine cause a number of changes in dopamine cells, some of which result in a decrease in their vulnerability to subsequent oxidative stress. These observations may provide insights into the development of new therapies for prevention or treatment of PD

Melanosomes in pigmented epithelia maintain eye lens transparency during zebrafish embryonic development

Altered levels of trace elements are associated with increased oxidative stress that is eventually responsible for pathologic conditions. Oxidative stress has been proposed to be involved in eye diseases, including cataract formation. We visualized the distribution of metals and other trace elements in the eye of zebrafish embryos by micro X-ray fluorescence (mu-XRF) imaging. Many elements showed highest accumulation in the retinal pigment epithelium (RPE) of the zebrafish embryo. Knockdown of the zebrafish brown locus homologues tyrp1a/b eliminated accumulation of these elements in the RPE, indicating that they are bound by mature melanosomes. Furthermore, albino (slc45a2) mutants, which completely lack melanosomes, developed abnormal lens reflections similar to the congenital cataract caused by mutation of the myosin chaperon Unc45b, and an in situ spin trapping assay revealed increased oxidative stress in the lens of albino mutants. Finally transplanting a wildtype lens into an albino mutant background resulted in cataract formation. These data suggest that melanosomes in pigment epithelial cells protect the lens from oxidative stress during embryonic development, likely by buffering trace elements.Peer reviewe