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

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

A more active lifestyle in persons with a recent spinal cord injury benefits physical fitness and health

Study design:A prospective cohort study. Objectives:To study the longitudinal relationship between objectively measured everyday physical activity level, and physical fitness and lipid profile in persons with a recent spinal cord injury (SCI).Setting:A rehabilitation centre in the Netherlands and the participant's home environment. Methods:Data of 30 persons with a recent SCI were collected at the start of active rehabilitation, 3 months later, at discharge from inpatient rehabilitation, and 1 year after discharge. Physical activity level (duration of dynamic activities as % of 24 h) was measured with an accelerometry-based activity monitor. Regarding physical fitness, peak oxygen uptake (VO2peak) and peak power output (POpeak) were determined with a maximal wheelchair exercise test, and upper extremity muscle strength was measured with a handheld dynamometer. Fasting blood samples were taken to determine the lipid profile. Results:An increase in physical activity level was significantly related to an increase in VO2peak and POpeak, and an increase in physical activity level favourably affected the lipid profile. A nonsignificant relation was found with muscle strength. Conclusion:Everyday physical activity seems to have an important role in the fitness and health of persons with a recent SCI. An increase in physical activity level was associated with an increase in physical fitness and with a lower risk of cardiovascular disease.Spinal Cord advance online publication, 6 December 2011; doi:10.1038/sc.2011.152

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

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

A slice of AdS_5 as the large N limit of Seiberg duality

A slice of AdS_5 is used to provide a 5D gravitational description of 4D strongly-coupled Seiberg dual gauge theories. An (electric) SU(N) gauge theory in the conformal window at large N is described by the 5D bulk, while its weakly coupled (magnetic) dual is confined to the IR brane. This framework can be used to construct an N = 1 MSSM on the IR brane, reminiscent of the original Randall-Sundrum model. In addition, we use our framework to study strongly-coupled scenarios of supersymmetry breaking mediated by gauge forces. This leads to a unified scenario that connects the extra-ordinary gauge mediation limit to the gaugino mediation limit in warped space.Comment: 47 Pages, axodraw4j.st

Cleavage of von Willebrand Factor by Granzyme M Destroys Its Factor VIII Binding Capacity

Von Willebrand factor (VWF) is a pro-hemostatic multimeric plasma protein that promotes platelet aggregation and stabilizes coagulation factor VIII (FVIII) in plasma. The metalloproteinase ADAMTS13 regulates the platelet aggregation function of VWF via proteolysis. Severe deficiency of ADAMTS13 is associated with thrombotic thrombocytopenic purpura, but does not always correlate with its clinical course. Therefore, other proteases could also be important in regulating VWF activity. In the present study, we demonstrate that VWF is cleaved by the cytotoxic lymphocyte granule component granzyme M (GrM). GrM cleaved both denaturated and soluble plasma-derived VWF after Leu at position 276 in the D3 domain. GrM is unique in that it did not affect the multimeric size and pro-hemostatic platelet aggregation ability of VWF, but instead destroyed the binding of VWF to FVIII in vitro. In meningococcal sepsis patients, we found increased plasma GrM levels that positively correlated with an increased plasma VWF/FVIII ratio in vivo. We conclude that, next to its intracellular role in triggering apoptosis, GrM also exists extracellularly in plasma where it could play a physiological role in controlling blood coagulation by determining plasma FVIII levels via proteolytic processing of its carrier VWF

Gene-modified T cells for adoptive immunotherapy of renal cell cancer maintain transgene-specific immune functions in vivo

Abstract BACKGROUND: We have treated three patients with carboxy-anhydrase-IX (CAIX) positive metastatic renal cell cancer (RCC) by adoptive transfer of autologous T-cells that had been gene-transduced to express a single-chain antibody-G250 chimeric receptor [scFv(G250)], and encountered liver toxicity necessitating adaptation of the treatment protocol. Here, we investigate whether or not the in vivo activity of the infused scFv(G250)(+) T cells is reflected by changes of selected immune parameters measured in peripheral blood. METHODS: ScFv(G250)-chimeric receptor-mediated functions of peripheral blood mononuclear cells (PBMC) obtained from three patients during and after treatment were compared to the same functions of scFv(G250)(+) T lymphocytes prior to infusion, and were correlated with plasma cytokine levels. RESULTS: Prior to infusion, scFv(G250)(+) T lymphocytes showed in vitro high levels of scFv(G250)-chimeric receptor-mediated functions such as killing of CAIX(+) RCC cell lines and cytokine production upon exposure to these cells. High levels of IFN-gamma were produced, whilst production of TNF-alpha, interleukin-4 (IL-4), IL-5 and IL-10 was variable and to lower levels, and that of IL-2 virtually absent. PBMC taken from patients during therapy showed lower levels of in vitro scFv(G250)-receptor-mediated functions as compared to pre-infusion, whilst IFN-gamma was the only detectable cytokine upon in vitro PBMC exposure to CAIX. During treatment, plasma levels of IFN-gamma increased only in the patient with the most prominent liver toxicity. IL-5 plasma levels increased transiently during treatment in all patients, which may have been triggered by the co-administration of IL-2. CONCLUSION: ScFv(G250)-receptor-mediated functions of the scFv(G250)(+) T lymphocytes are, by and large, preserved in vivo upon administration, and may be reflected by fluctuations in plasma IFN-gamma levels

Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy

BACKGROUND : The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12 and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients. METHODS : In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of two public hospitals in South Africa were approached for participation. Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency (defined by concentrations <150 pmol/L) was determined. Those with NTSS-6 scores >6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple logistic regression was used to determine risk factors for vitamin B12 deficiency. RESULTS : Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no difference in presence of neuropathy between those with normal and deficient vitamin levels (36.8 % vs. 32.3 %, P = 0.209). Vitamin B12 levels and NTSS-6 scores were not correlated (Spearman’s rho =0.056, P = 0.54). HbA1c (mmol/mol) (OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI: 0.13 to 0.92, P = 0.033) were risk factors significantly associated with vitamin B12 deficiency. Metformin daily dose (gram) showed borderline significance (OR = 1.96, 95 % CI: 0.99 to 3.88, P = 0.053). CONCLUSIONS : Close to third of metformin-treated T2DM patients had vitamin B12 deficiency. The deficiency was not associated with peripheral neuropathy. Black race was a protective factor for vitamin B12 deficiency.The Department of Pharmacology, University of Pretoriahttp://bmcpharmacoltoxicol.biomedcentral.comam2017Internal MedicinePharmacolog

Projected Prevalence of Inadequate Nutrient Intakes in Europe

Background: The purpose of this study was to analyze the prevalence of nutrient intake inadequacy in Europe, applying the Nordic Nutritional Recommendations in the context of the EURRECA Network of Excellence. Methods: Nutrient data was obtained from the European Nutrition and Health Report II. Those nutritional surveys using a validated food frequency questionnaire or diet history and a food diary/register with at least 7 days of registers or with an adjustment for intraindividual variability were included. The nutrients analyzed were: vitamin C, vitamin D, vitamin B-12, folic acid, calcium, iron, zinc, selenium, copper, and iodine. The estimated average requirement cut point was applied to estimate inadequacy. The Nordic and Institute of Medicine nutrient recommendations were used as references. Results: The mean prevalence of inadequacy was below 11% for zinc, iron, and vitamin B-12 (only in the elderly), and it was 11-20% for copper in adults and the elderly and for vitamin B-12 in adults and vitamin C in the elderly. The prevalence was above 20% for vitamin D, folic acid, calcium, selenium, and iodine in adults and the elderly and for vitamin C in adults. Conclusions: Vitamin C, vitamin D, folic acid, calcium, selenium, and iodine were the nutrients showing a higher prevalence of inadequate intakes in Europe. Copyright (C) 2011 S. Karger AG, Base