Physiological-social score (PMEWS) vs. CURB-65 to triage pandemic influenza: a comparative validation study using community-acquired pneumonia as a proxy

BACKGROUND: An influenza pandemic may increase Emergency Department attendance 7-fold. In the absence of a validated "flu score" to assess severity and assist triage decisions from primary into secondary care, current UK draft management recommendations have suggested the use of CURB-65 and chest X-ray as a proxy. We developed the Pandemic Medical Early Warning Score (PMEWS) to track and triage flu patients, taking into account physiological and social factors and without requiring laboratory or radiology services. METHODS: Validation of the PMEWS score against an unselected group of patients presenting and admitted to an urban UK teaching hospital with community acquired pneumonia. Comparison of PMEWS performance against CURB-65 for three outcome measures: need for admission, admission to high dependency or intensive care, and inpatient mortality using area under ROC curve (AUROC) and the Hanley-McNeil method of comparison. RESULTS: PMEWS was a better predictor of need for admission (AUROC 0.944) and need of higher level of care (AUROC 0.83) compared with CURB-65 (AUROCs 0.881 and 0.640 respectively) but was not as good a predictor of subsequent inpatient mortality (AUROC 0.663). CONCLUSION: Although further validation against other disease datasets as a proxy for pandemic flu is required, we show that PMEWS is rapidly applicable for triage of large numbers of flu patients to self-care, hospital admission or HDU/ICU care. It is scalable to reflect changing admission thresholds that will occur during a pandemic

Hyponatremia and hospital outcomes among patients with pneumonia: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Community-acquired (CAP) and nosocomial pneumonias contribute substantially to morbidity and hospital resource utilization. Hyponatremia, occurring in >1/4 of patients with CAP, is associated with greater disease severity and worsened outcomes.</p> <p>Methods</p> <p>To explore how hyponatremia is associated with outcomes in hospitalized patients with pneumonia, we analyzed a large administrative database with laboratory component from January 2004 to December 2005. Hyponatremia was defined as at least two [Na⁺] < 135 mEq/L within 24 hours of admission value.</p> <p>Results</p> <p>Of 7,965 patients with pneumonia, 649 (8.1%) with hyponatremia were older (72.4 ± 15.7 vs. 68.0 ± 22.0, p < 0.01), had a higher mean Deyo-Charlson Comorbidity Index Score (1.7 ± 1.7 vs. 1.6 ± 1.6, p = 0.02), and higher rates of ICU (10.0% vs. 6.3%, p < 0.001) and MV (3.9% vs. 2.3%, p = 0.01) in the first 48 hours of hospitalization than patients with normal sodium. Hyponatremia was associated with an increased ICU (6.3 ± 5.6 vs. 5.3 ± 5.1 days, p = 0.07) and hospital lengths of stay (LOS, 7.6 ± 5.3 vs. 7.0 ± 5.2 days, p < 0.001) and a trend toward increased hospital mortality (5.4% vs. 4.0%, p = 0.1). After adjusting for confounders, hyponatremia was associated with an increased risk of ICU (OR 1.58, 95% CI 1.20–2.08), MV (OR 1.75 95% CI 1.13–2.69), and hospital death (OR 1.3, 95% CI 0.90–1.87) and with increases of 0.8 day to ICU and 0.3 day to hospital LOS, and over $1,300 to total hospital costs.</p> <p>Conclusion</p> <p>Hyponatremia is common among hospitalized patients with pneumonia and is associated with worsened clinical and economic outcomes. Studies in this large population are needed to explore whether prompt correction of [Na⁺] may impact these outcomes.</p

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF &lt;5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Estimating Loss to Follow-Up in HIV-Infected Patients on Antiretroviral Therapy: The Effect of the Competing Risk of Death in Zambia and Switzerland

BACKGROUND: Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland. METHODS AND FINDINGS: HIV-infected patients aged ≥18 years who started ART 2004-2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ≥350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naïve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up. CONCLUSIONS: In ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings

A warm Jet in a cold ocean

Unprecedented quantities of heat are entering the Pacific sector of the Arctic Ocean through Bering Strait, particularly during summer months. Though some heat is lost to the atmosphere during autumn cooling, a significant fraction of the incoming warm, salty water subducts (dives beneath) below a cooler fresher layer of near-surface water, subsequently extending hundreds of kilometers into the Beaufort Gyre. Upward turbulent mixing of these sub-surface pockets of heat is likely accelerating sea ice melt in the region. This Pacific-origin water brings both heat and unique biogeochemical properties, contributing to a changing Arctic ecosystem. However, our ability to understand or forecast the role of this incoming water mass has been hampered by lack of understanding of the physical processes controlling subduction and evolution of this this warm water. Crucially, the processes seen here occur at small horizontal scales not resolved by regional forecast models or climate simulations; new parameterizations must be developed that accurately represent the physics. Here we present novel high resolution observations showing the detailed process of subduction and initial evolution of warm Pacific-origin water in the southern Beaufort Gyre

Mechanisms Promoting the Long-Term Persistence of a Wolbachia Infection in a Laboratory-Adapted Population of Drosophila melanogaster

Intracellular bacteria of the genus Wolbachia are widespread endosymbionts across diverse insect taxa. Despite this prevalence, our understanding of how Wolbachia persists within populations is not well understood. Cytoplasmic incompatibility (CI) appears to be an important phenotype maintaining Wolbachia in many insects, but it is believed to be too weak to maintain Wolbachia in Drosophila melanogaster, suggesting that Wolbachia must also have other effects on this species. Here we estimate the net selective effect of Wolbachia on its host in a laboratory-adapted population of D. melanogaster, to determine the mechanisms leading to its persistence in the laboratory environment. We found i) no significant effects of Wolbachia infection on female egg-to-adult survival or adult fitness, ii) no reduced juvenile survival in males, iii) substantial levels of CI, and iv) a vertical transmission rate of Wolbachia higher than 99%. The fitness of cured females was, however, severely reduced (a decline of 37%) due to CI in offspring. Taken together these findings indicate that Wolbachia is maintained in our laboratory environment due to a combination of a nearly perfect transmission rate and substantial CI. Our results show that there would be strong selection against females losing their infection and producing progeny free from Wolbachia

Formalization of the classification pattern: Survey of classification modeling in information systems engineering

Formalization is becoming more common in all stages of the development of information systems, as a better understanding of its benefits emerges. Classification systems are ubiquitous, no more so than in domain modeling. The classification pattern that underlies these systems provides a good case study of the move towards formalization in part because it illustrates some of the barriers to formalization; including the formal complexity of the pattern and the ontological issues surrounding the ‘one and the many’. Powersets are a way of characterizing the (complex) formal structure of the classification pattern and their formalization has been extensively studied in mathematics since Cantor’s work in the late 19th century. One can use this formalization to develop a useful benchmark. There are various communities within Information Systems Engineering (ISE) that are gradually working towards a formalization of the classification pattern. However, for most of these communities this work is incomplete, in that they have not yet arrived at a solution with the expressiveness of the powerset benchmark. This contrasts with the early smooth adoption of powerset by other Information Systems communities to, for example, formalize relations. One way of understanding the varying rates of adoption is recognizing that the different communities have different historical baggage. Many conceptual modeling communities emerged from work done on database design and this creates hurdles to the adoption of the high level of expressiveness of powersets. Another relevant factor is that these communities also often feel, particularly in the case of domain modeling, a responsibility to explain the semantics of whatever formal structures they adopt. This paper aims to make sense of the formalization of the classification pattern in ISE and surveys its history through the literature; starting from the relevant theoretical works of the mathematical literature and gradually shifting focus to the ISE literature. The literature survey follows the evolution of ISE’s understanding of how to formalize the classification pattern. The various proposals are assessed using the classical example of classification; the Linnaean taxonomy formalized using powersets as a benchmark for formal expressiveness. The broad conclusion of the survey is that (1) the ISE community is currently in the early stages of the process of understanding how to formalize the classification pattern, particularly in the requirements for expressiveness exemplified by powersets and (2) that there is an opportunity to intervene and speed up the process of adoption by clarifying this expressiveness. Given the central place that the classification pattern has in domain modeling, this intervention has the potential to lead to significant improvements.The UK Engineering and Physical Sciences Research Council (grant EP/K009923/1)