Mortality risk for different presenting complaints amongst older patients assessed with the Manchester triage system

Purpose: Older people often present to the Emergency Department with nonspecific complaints. We aimed (1) to examine characteristics of older patients presenting to the ED triaged with the presentational flowchart ‘unwell adult’ of the Manchester triage system (MTS) and (2) to assess the different mortality and admission rates among triage categories. Methods: Retrospective cohort study including all consecutive patients aged 70 years and older who visited the ED of a tertiary care hospital in the Netherlands during a 1-year period. The primary outcome was 30-day mortality. Secondary outcomes were 7-day mortality, hospital admission and ED length of stay. Results: 4255 patients were included in this study. Mean age was 78 years (IQR 73.9–83.4) and 2098 were male (49.3%). The MTS presentational flowchart ‘unwell adult’ was the most commonly used flowchart (n = 815, 19.3%). After the infrequent flowchart ‘major trauma’ (n = 9, 13.8%), ‘unwell adult’ had the highest 30-day mortality (n = 88, 10.8%). When compared to all other flowcharts, patients assigned as ‘unwell adult’ have significantly higher 30-day mortality rates (OR 1.89 (95%CI 1.46–2.46), p = < 0.001), also when adjusted for age, gender and triage priority (OR 1.75 (95%CI 1.32–2.31), p = < 0.001). Patients from the ‘unwell adult’ flowchart had the highest hospital admission rate (n = 540, 66.3%), and had among the longest ED length of stay. Conclusions: Older ED patients are most commonly assigned the presentational flowchart ‘unwell adult’ when using the MTS. Patients in this category have the highest non-trauma mortality and highest hospital admission rates when compared to other presenting complaints

Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo

<p>Abstract</p> <p>Background</p> <p>The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown.</p> <p>Results</p> <p>In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection.</p> <p>Conclusion</p> <p>Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection <it>in vivo</it>.</p

An inhomogeneous toy-model of the quantum gravity with explicitly evolvable observables

An inhomogeneous (1+1)-dimensional model of the quantum gravity is considered. It is found, that this model corresponds to a string propagating against some curved background space. The quantization scheme including the Wheeler-DeWitt equation and the "particle on a sphere" type of the gauge condition is suggested. In the quantization scheme considered, the "problem of time" is solved by building of the quasi-Heisenberg operators acting in a space of solutions of the Wheeler-DeWitt equation and the normalization of the wave function corresponds to the Klein-Gordon type. To analyze the physical consequences of the scheme, a (1+1)-dimensional background space is considered for which a classical solution is found and quantized. The obtained estimations show the way to solution of the cosmological constant problem, which consists in compensation of the zero-point oscillations of the matter fields by the quantum oscillations of the scale factor. Along with such a compensation, a slow global evolution of a background corresponding to an universe expansion exists.Comment: 18 page

Non-supersymmetric heterotic model building

We investigate orbifold and smooth Calabi-Yau compactifications of the non-supersymmetric heterotic SO(16)xSO(16) string. We focus on such Calabi-Yau backgrounds in order to recycle commonly employed techniques, like index theorems and cohomology theory, to determine both the fermionic and bosonic 4D spectra. We argue that the N=0 theory never leads to tachyons on smooth Calabi-Yaus in the large volume approximation. As twisted tachyons may arise on certain singular orbifolds, we conjecture that such tachyonic states are lifted in the full blow-up. We perform model searches on selected orbifold geometries. In particular, we construct an explicit example of a Standard Model-like theory with three generations and a single Higgs field.Comment: 1+30 pages latex, 11 tables; v2: references and minor revisions added, matches version published in JHE

Molecular mechanisms that distinguish TFIID housekeeping from regulatable SAGA promoters

An important distinction is frequently made between constitutively expressed housekeeping genes versus regulated genes. Although generally characterized by different DNA elements, chromatin architecture and cofactors, it is not known to what degree promoter classes strictly follow regulatability rules and which molecular mechanisms dictate such differences. We show that SAGA-dominated/wTATA-box promoters are more responsive to changes in the amount of activator, even compared to TFIID/TATA-like promoters that depend on the same activator Hsf1. Regulatability is therefore an inherent property of promoter class. Further analyses show that SAGA/TATA-box promoters are more dynamic because TATA-binding protein recruitment through SAGA is susceptible to removal by Mot1. In addition, the nucleosome configuration upon activator depletion shifts on SAGA/TATA-box promoters and seems less amenable to preinitiation complex formation. The results explain the fundamental difference between housekeeping and regulatable genes, revealing an additional facet of combinatorial control: an activator can elicit a different response dependent on core promoter class

Time for T? Immunoinformatics addresses the challenges of vaccine design for neglected tropical and emerging infectious diseases

Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere

Prediction of 90-day mortality in older patients after discharge from an emergency department: a retrospective follow-up study

Background: Older people frequently attend the emergency department (ED) and have a high risk of poor outcome as compared to their younger counterparts. Our aim was to study routinely collected clinical parameters as predictors of 90-day mortality in older patients attending our ED. Methods: We conducted a retrospective follow-up study at the Leiden University Medical Center (The Netherlands) among patients aged 70 years or older attending the ED in 2012. Predictors were age, gender, time and way of arrival, presenting complaint, consulting medical specialty, vital signs, pain score and laboratory testing. Cox regression analyses were performed to analyse the association between these predictors and 90-day mortality. Results: Three thousand two hundred one unique patients were eligible for inclusion. Ninety-day mortality was 10.5 % for the total group. Independent predictors of mortality were age (hazard ratio [HR] 1.06, 95 % confidence interval [95 % CI] 1.04-1.08), referral from another hospital (HR 2.74, 95 % CI 1.22-6.11), allocation to a non-surgical specialty (HR: 1.55, 95 % CI 1.13-2.14), increased respiration rate (HR up to 2.21, 95 % CI 1.25-3.92), low oxygen saturation (HR up to 1.96, 95 % CI 1.19-3.23), hypothermia (HR 2.27, 95 % CI 1.28-4.01), fever (HR 0.43, 95 % CI 0.24-0.75), high pain score (HR 1.55, 95 % CI 1.03-2.32) and the indication to perform laboratory testing (HR 3.44, 95 % CI 2.13-5.56). Conclusions: Routinely collected parameters at the ED can predict 90-day mortality in older patients presenting to the ED. This study forms the first step towards creating a new and simple screening tool to predict and improve health outcome in acutely presenting older patients

Predicting mortality in acutely hospitalized older patients: a retrospective cohort study

Acutely hospitalized older patients have an increased risk of mortality, but at the moment of presen- tation this risk is difficult to assess. Early identification of patients at high risk might increase the awareness of the physician, and enable tailored decision-making. Existing screening instruments mainly use either geriatric factors or severity of disease for prognostication. Predictive perfor- mance of these instruments is moderate, which hampers successive interventions. We conducted a retrospective cohort study among all patients aged 70 years and over who were acutely hospitalized in the Acute Medical Unit of the Leiden University Medical Center, the Netherlands in 2012. We developed a prediction model for 90-day mor- tality that combines vital signs and laboratory test results reflecting severity of disease with geriatric factors, repre- sented by comorbidities and number of medications. Among 517 patients, 94 patients (18.2 %) died within 90 days after admission. Six predictors of mortality were included in a model for mortality: oxygen saturation, Charlson comorbidity index, thrombocytes, urea, C-reac- tive protein and non-fasting glucose. The prediction model performs satisfactorily with an 0.738 (0.667–0.798). Using this model, 53 % of the patients in the highest risk decile ( N = 51) were deceased within 90 days. In conclusion, we are able to predict 90-day mortality in acutely hospitalized older patients using a model with directly available clinical data describing disease severity and geriatric factors. After further validation, such a model might be used in clinical decision making in older patients