The use of different sepsis risk stratification tools on the wards and in emergency departments uncovers different mortality risks: results of the three Welsh national multicenter point-prevalence studies

OBJECTIVES: To compare the performance of Sequential Organ Failure Assessment, systemic inflammatory response syndrome, Red Flag Sepsis, and National Institute of Clinical Excellence sepsis risk stratification tools in the identification of patients at greatest risk of mortality from sepsis in nonintensive care environments. DESIGN: Secondary analysis of three annual 24-hour point-prevalence study periods. SETTING: The general wards and emergency departments of 14 acute hospitals across Wales. Studies were conducted on the third Wednesday of October in 2017, 2018, and 2019. PATIENTS: We screened all patients presenting to the emergency department and on the general wards. MEASUREMENTS AND MAIN RESULTS: We recruited 1,271 patients, of which 724 (56.9%) had systemic inflammatory response syndrome greater than or equal to 2, 679 (53.4%) had Sequential Organ Failure Assessment greater than or equal to 2, and 977 (76.9%) had Red Flag Sepsis. When stratified according to National Institute of Clinical Excellence guidelines, 450 patients (35.4%) were in the “High risk” category in comparison with 665 (52.3%) in “Moderate to High risk” and 156 (12.3%) in “Low risk” category. In a planned sensitivity analysis, we found that none of the tools accurately predicted mortality at 90 days, and Sequential Organ Failure Assessment and National Institute of Clinical Excellence tools showed only moderate discriminatory power for mortality at 7 and 14 days. Furthermore, we could not find any significant correlation with any of the tools at any of the mortality time points. CONCLUSIONS: Our data suggest that the sepsis risk stratification tools currently utilized in emergency departments and on the general wards do not predict mortality adequately. This is illustrated by the disparity in mortality risk of the populations captured by each instrument, as well as the weak concordance between them. We propose that future studies on the development of sepsis identification tools should focus on identifying predicator values of both the short- and long-term outcomes of sepsis

Publisher Correction: Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease:Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper

Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease

Iron is suggested to play a detrimental role in the progression of chronic kidney disease (CKD). The kidney recycles iron back into the circulation. However, the localization of proteins relevant for physiological tubular iron handling and their potential role in CKD remain unclear. We examined associations between iron deposition, expression of iron handling proteins and tubular injury in kidney biopsies from CKD patients and healthy controls using immunohistochemistry. Iron was deposited in proximal (PT) and distal tubules (DT) in 33% of CKD biopsies, predominantly in pathologies with glomerular dysfunction, but absent in controls. In healthy kidney, PT contained proteins required for iron recycling including putative iron importers ZIP8, ZIP14, DMT1, iron storage proteins L- and H-ferritin and iron exporter ferroportin, while DT only contained ZIP8, ZIP14, and DMT1. In CKD, iron deposition associated with increased intensity of iron importers (ZIP14, ZIP8), storage proteins (L-, H-ferritin), and/or decreased ferroportin abundance. This demonstrates that tubular iron accumulation may result from increased iron uptake and/or inadequate iron export. Iron deposition associated with oxidative injury as indicated by heme oxygenase-1 abundance. In conclusion, iron deposition is relatively common in CKD, and may result from altered molecular iron handling and may contribute to renal injury

SPHEREx: NASA's near-infrared spectrophotometric all-sky survey

SPHEREx, the Spectro-Photometer for the History of the Universe, Epoch of Reionization, and ices Explorer, is a NASA MIDEX mission planned for launch in 2024. SPHEREx will carry out the first all-sky spectral survey at wavelengths between 0.75µm and 5µm with spectral resolving power ~40 between 0.75 and 3.8µm and ~120 between 3.8 and 5µm At the end of its two-year mission, SPHEREx will provide 0.75-to-5µm spectra of each 6.”2 x 6.”2 pixel on the sky - 14 billion spectra in all. This paper updates an earlier description of SPHEREx presenting changes made during the mission's Preliminary Design Phase, including a discussion of instrument integration and test ow and a summary of the data processing, analysis, and distribution plans

Real world patterns of antimicrobial use and microbiology investigations in patients with sepsis outside the Critical Care Unit: Secondary analysis of three nation-wide point prevalence studies

Recent description of the microbiology of sepsis on the wards or information on the real-life antibiotic choices used in sepsis is lacking. There is growing concern of the indiscriminate use of antibiotics and omission of microbiological investigations in the management of septic patients. We performed a secondary analysis of three annual 24-h point-prevalence studies on the general wards across all Welsh acute hospitals in years 2016–2018. Data were collected on patient demographics, as well as radiological, laboratory and microbiological data within 48-h of the study. We screened 19,453 patients over the three 24 h study periods and recruited 1252 patients who fulfilled the entry criteria. 775 (64.9%) patients were treated with intravenous antibiotics. Only in 33.65% (421/1252) of all recruited patients did healthcare providers obtain blood cultures; in 25.64% (321/1252) urine cultures; in 8.63% (108/1252) sputum cultures; in 6.79% (85/1252) wound cultures; in 15.25% (191/1252) other cultures. Out of the recruited patients, 59.1% (740/1252) fulfilled SEPSIS-3 criteria. Patients with SEPSIS-3 criteria were significantly more likely to receive antibiotics than the non-septic cohort (p < 0.0001). In a multivariable regression analysis increase in SOFA score, increased number of SIRS criteria and the use of the official sepsis screening tool were associated with antibiotic administration, however obtaining microbiology cultures was not. Our study shows that antibiotics prescription practice is not accompanied by microbiological investigations. A significant proportion of sepsis patients are still at risk of not receiving appropriate antibiotics treatment and microbiological investigations; this may be improved by a more thorough implementation of sepsis screening tools

Four consecutive yearly point-prevalence studies in Wales indicate lack of improvement in sepsis care on the wards

The ‘Sepsis Six’ bundle was promoted as a deliverable tool outside of the critical care settings, but there is very little data available on the progress and change of sepsis care outside the critical care environment in the UK. Our aim was to compare the yearly prevalence, outcome and the Sepsis Six bundle compliance in patients at risk of mortality from sepsis in non-intensive care environments. Patients with a National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled into four yearly 24-h point prevalence studies, carried out in fourteen hospitals across Wales from 2016 to 2019. We followed up patients to 30 days between 2016–2019 and to 90 days between 2017 and 2019. Out of the 26,947 patients screened 1651 fulfilled inclusion criteria and were recruited. The full ‘Sepsis Six’ care bundle was completed on 223 (14.0%) occasions, with no significant difference between the years. On 190 (11.5%) occasions none of the bundle elements were completed. There was no significant correlation between bundle element compliance, NEWS or year of study. One hundred and seventy (10.7%) patients were seen by critical care outreach; the ‘Sepsis Six’ bundle was completed significantly more often in this group (54/170, 32.0%) than for patients who were not reviewed by critical care outreach (168/1385, 11.6%; p < 0.0001). Overall survival to 30 days was 81.7% (1349/1651), with a mean survival time of 26.5 days (95% CI 26.1–26.9) with no difference between each year of study. 90-day survival for years 2017–2019 was 74.7% (949/1271), with no difference between the years. In multivariate regression we identified older age, heart failure, recent chemotherapy, higher frailty score and do not attempt cardiopulmonary resuscitation orders as significantly associated with increased 30-day mortality. Our data suggests that despite efforts to increase sepsis awareness within the NHS, there is poor compliance with the sepsis care bundles and no change in the high mortality over the study period. Further research is needed to determine which time-sensitive ward-based interventions can reduce mortality in patients with sepsis and how can these results be embedded to routine clinical practice

Biotic and environmental dynamics through the Late Jurassic-Early Cretaceous transition: evidence for protracted faunal and ecological turnover

The Late Jurassic to Early Cretaceous interval represents a time of environmental upheaval and cataclysmic events, combined with disruptions to terrestrial and marine ecosystems. Historically, the Jurassic/Cretaceous (J/K) boundary was classified as one of eight mass extinctions. However, more recent research has largely overturned this view, revealing a much more complex pattern of biotic and abiotic dynamics than has previously been appreciated. Here, we present a synthesis of our current knowledge of Late Jurassic–Early Cretaceous events, focusing particularly on events closest to the J/K boundary. We find evidence for a combination of short-term catastrophic events, large-scale tectonic processes and environmental perturbations, and major clade interactions that led to a seemingly dramatic faunal and ecological turnover in both the marine and terrestrial realms. This is coupled with a great reduction in global biodiversity which might in part be explained by poor sampling. Very few groups appear to have been entirely resilient to this J/K boundary ‘event’, which hints at a ‘cascade model’ of ecosystem changes driving faunal dynamics. Within terrestrial ecosystems, larger, more-specialised organisms, such as saurischian dinosaurs, appear to have suffered the most. Medium-sized tetanuran theropods declined, and were replaced by larger-bodied groups, and basal eusauropods were replaced by neosauropod faunas. The ascent of paravian theropods is emphasised by escalated competition with contemporary pterosaur groups, culminating in the explosive radiation of birds, although the timing of this is obfuscated by biases in sampling. Smaller, more ecologically diverse terrestrial non-archosaurs, such as lissamphibians and mammaliaforms, were comparatively resilient to extinctions, instead documenting the origination of many extant groups around the J/K boundary. In the marine realm, extinctions were focused on low-latitude, shallow marine shelf-dwelling faunas, corresponding to a significant eustatic sea-level fall in the latest Jurassic. More mobile and ecologically plastic marine groups, such as ichthyosaurs, survived the boundary relatively unscathed. High rates of extinction and turnover in other macropredaceous marine groups, including plesiosaurs, are accompanied by the origin of most major lineages of extant sharks. Groups which occupied both marine and terrestrial ecosystems, including crocodylomorphs, document a selective extinction in shallow marine forms, whereas turtles appear to have diversified. These patterns suggest that different extinction selectivity and ecological processes were operating between marine and terrestrial ecosystems, which were ultimately important in determining the fates of many key groups, as well as the origins of many major extant lineages. We identify a series of potential abiotic candidates for driving these patterns, including multiple bolide impacts, several episodes of flood basalt eruptions, dramatic climate change, and major disruptions to oceanic systems. The J/K transition therefore, although not a mass extinction, represents an important transitional period in the co-evolutionary history of life on Earth

The gas engineer of the last century. The 4th Thomas Hawksley lecture.** first Thomas Hawksley lecture, by E. B. Ellington, proceedings, I.Mech.E., 1913, page 1215. second lecture, by W. B. Bryan, 1914, page 811. Third lecture, by Dugald Clerk, D.Sc., F.R.S., 1915, page 591. The gas engineer of the last century.

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The International Diabetes Federation : losing its credibility by partnering with Nestle?

The International Diabetes Federation (IDF) is an umbrella organisation of more than 200 national diabetes associations in over 160 countries, and states its mission as being “to promote diabetes care, prevention and a cure worldwide”. In pursuing this mission, it can proudly point to many highly successful initiatives, helping to raise awareness, advocate for and guide clinical and public health action, and to build alliances for the prevention and control of diabetes and other chronic non-communicable diseases (NCDs) worldwide. Unfortunately its partnering with Nestlé, announced on Nestlé's website at the end of April,1 is in our view a serious misjudgment, the long-term effect of which will be contrary to IDF's mission and bad for public health