Two lineages of Salmonella enterica serovar Typhimurium (S. Typhimurium) of multi-locus sequence type ST313 have been linked with the emergence of invasive Salmonella disease across sub-Saharan ...Africa. The expansion of these lineages has a temporal association with the HIV pandemic and antibiotic usage. We analysed the whole genome sequence of 129 ST313 isolates representative of the two lineages and found evidence of lineage-specific genome degradation, with some similarities to that observed in S. Typhi. Individual ST313 S. Typhimurium isolates exhibit a distinct metabolic signature and modified enteropathogenesis in both a murine and cattle model of colitis, compared to S. Typhimurium outside of the ST313 lineages. These data define phenotypes that distinguish ST313 isolates from other S. Typhimurium and may represent adaptation to a distinct pathogenesis and lifestyle linked to an-immuno-compromised human population.
This study sought to compare a continuous infusion diuretic strategy versus an intermittent bolus diuretic strategy, with the addition of low-dose dopamine (3 μg/kg/min) in the treatment of ...hospitalized patients with heart failure with preserved ejection fraction (HFpEF).
HFpEF patients are susceptible to development of worsening renal function (WRF) when hospitalized with acute heart failure; however, inpatient treatment strategies to achieve safe and effective diuresis in HFpEF patients have not been studied to date.
In a prospective, randomized, clinical trial, 90 HFpEF patients hospitalized with acute heart failure were randomized within 24 h of admission to 1 of 4 treatments: 1) intravenous bolus furosemide administered every 12 h; 2) continuous infusion furosemide; 3) intermittent bolus furosemide with low-dose dopamine; and 4) continuous infusion furosemide with low-dose dopamine. The primary endpoint was percent change in creatinine from baseline to 72 h. Linear and logistic regression analyses with tests for interactions between diuretic and dopamine strategies were performed.
Compared to intermittent bolus strategy, the continuous infusion strategy was associated with higher percent increase in creatinine (continuous infusion: 16.01%; 95% confidence interval CI: 8.58% to 23.45% vs. intermittent bolus: 4.62%; 95% CI: −1.15% to 10.39%; p = 0.02). Low-dose dopamine had no significant effect on percent change in creatinine (low-dose dopamine: 12.79%; 95% CI: 5.66% to 19.92%, vs. no-dopamine: 8.03%; 95% CI: 1.44% to 14.62%; p = 0.33). Continuous infusion was also associated with greater risk of WRF than intermittent bolus (odds ratio OR: 4.32; 95% CI: 1.26 to 14.74; p = 0.02); no differences in WRF risk were seen with low-dose dopamine. No significant interaction was seen between diuretic strategy and low-dose dopamine (p > 0.10).
In HFpEF patients hospitalized with acute heart failure, low-dose dopamine had no significant impact on renal function, and a continuous infusion diuretic strategy was associated with renal impairment. (Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction ROPA-DOP; NCT01901809)
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IntroductionColorectal cancer is the fourth most common cancer in the UK and an important cause of cancer-related death. In 20% of patients, there is metastasis to the liver or beyond at the time of ...diagnosis. The management of synchronous disease is complex. Conventional surgery removes the colorectal primary first, followed by chemotherapy, with resection of liver metastases as a final step. Advances in the availability and safety of liver surgery, anaesthesia and critical care have made two alternative options feasible. The first is synchronous resection of the primary and liver metastases. The second is resection of the metastatic disease as the first step, termed the reverse or liver-first approach. Currently, evidence is inadequate to inform the selection of care pathway for patients with colorectal cancer and synchronous liver-limited metastases. Specifically, optimal pathways are not defined and there is a dearth of prospectively recorded cohort-defining factors influencing treatment selection or outcome.Methods and analysisColorectal cancer with Synchronous liver-limited Metastases: an Inception Cohort (CoSMIC) is an inception cohort study of patients with a new diagnosis of colorectal cancer with synchronous liver-limited metastases. The sequence of treatment received, and factors influencing treatment decisions, will be evaluated against European Society of Medical Oncology guidelines. Clinical data will be collected, and quality of life, morbidity, mortality and long-term outcome compared for different treatment sequences adjusted for prognostic factors. Disease-free survival or progression will be measured at 1, 2 and 5 years. A nested qualitative study will ascertain patient experiences and clinician perspectives on delivery of care.Ethics and disseminationThe full study protocol was independently peer reviewed by Professor Kees de Jong (University of Maastricht, Holland). CoSMIC has ethical approval from the National Health Service Research Ethics Committee (14/NW/1397). Results will be disseminated to healthcare professionals and patient groups, and may be used to design a definitive trial addressing areas of equipoise in treatment pathways, as well as optimising current pathways to improve outcomes and experiences.Trial registration numberNCT02456285, pre-results.
The incidence of temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (MTS) can be high in developing countries. Current diagnosis of MTS relies on structural MRI, which is generally ...unavailable in developing world settings. Given widespread effects on temporal lobe structure beyond hippocampal atrophy in TLE, the authors propose that CT volumetric analysis can be used in patient selection to help predict outcomes following resection.
Ten pediatric patients received preoperative CT scans and temporal resections at the CURE Children's Hospital of Uganda. Engel classification of seizure control was determined 12 months postoperatively. Temporal lobe volumes were measured from CT and from normative MR images using the Cavalieri method. Whole brain and fluid volumes were measured using particle filter segmentation. Linear discrimination analysis (LDA) was used to classify seizure outcome by temporal lobe volumes and normalized brain volume.
Epilepsy patients showed normal to small brain volumes and small temporal lobes bilaterally. A multivariate measure of the volume of each temporal lobe separated patients who were seizure free (Engel Class IA) from those with incomplete seizure control (Engel Class IB/IIB) with LDA (p<0.01). Temporal lobe volumes also separate normal subjects, patients with Engel Class IA outcomes, and patients with Class IB/IIB outcomes (p<0.01). Additionally, the authors demonstrated that age-normalized whole brain volume, in combination with temporal lobe volumes, may further improve outcome prediction (p<0.01).
This study shows strong evidence that temporal lobe and brain volume can be predictive of seizure outcome following temporal lobe resection, and that volumetric CT analysis of the temporal lobe may be feasible in lieu of structural MRI when the latter is unavailable. Furthermore, since the authors' methods are modality independent, these findings suggest that temporal lobe and normative brain volumes may further be useful in the selection of patients for temporal lobe resection when structural MRI is available.
Abstract
Background
Influenza can lead to severe outcomes among adults hospitalized with influenza, and causes substantial annual morbidity and mortality. We evaluated the performance of validated ...pneumonia severity indices in predicting severe influenza-associated outcomes.
Methods
We conducted a multicenter study within CDC’s Influenza Hospitalization Surveillance Network (FluSurv-NET) which included adults (≥ 18 years) hospitalized with laboratory-confirmed influenza during the 2017–18 influenza season. Medical charts were abstracted to obtain data on vital signs and laboratory values at admission on a stratified random sample of cases at a subset of hospitals at 11 network sites. Estimates were weighted to reflect the probability of selection. Cases were assigned to low- and high-risk groups based on the CURB-65 (‘Confusion, Urea, Respiratory rate, Blood pressure, Age ≥65’) index (high-risk cutoff = score ≥ 3), and the Pneumonia Severity Index (PSI) (high-risk cutoff = category V). We calculated area under receiver operating characteristic curves (AUROC), sensitivity, and specificity to estimate the performance of each index in predicting severe outcome categories: (1) intensive care unit (ICU) admission, 2) noninvasive mechanical ventilation (NIMV), (3) mechanical ventilation (MV), vasopressors, extracorporeal membrane oxygenation (ECMO) and (4) death.
Results
Among 27,523 adults hospitalized with influenza, 8665 (31%) were sampled for inclusion in this analysis; median age was 70 years and 92% had ≥ 1 chronic condition. A total of 1,366 (16%) were classified as high-risk by CURB-65 and 1,249 (14%) by PSI. Both indices had low discrimination for severe outcomes; the AUROC for CURB-65 ranged from 0.55 for ICU admission to 0.65 for death, and for PSI ranged from 0.58 for ICU admission to 0.73 for death. Risk status by CURB-65 was less sensitive than PSI in predicting MV, vasopressor, or ECMO usage as well as death (figure). The specificity of CURB-65 and PSI was similar against all outcomes (figure).
Conclusion
The CURB-65 and PSI indices performed poorly in predicting severe outcomes other than death; PSI had the best discrimination overall. Alternative approaches are needed to predict severe influenza-related outcomes and optimize clinical care.
Disclosures
All Authors: No reported Disclosures.
The majority of intracerebral haemorrhage patients present with markedly elevated blood pressure immediately after symptom onset. Management of blood pressure in the first 24 h is extremely ...controversial and lends itself to two competing rationales. There is some evidence that early treatment may improve outcome, potentially by reducing the rate of haematoma expansion. It is also possible that this will reduce cerebral blood flow and therefore exacerbate the cerebral injury, particularly in the region surrounding the haematoma. Only a trial that includes both randomisation of patients to two different blood pressure management strategies and actual measurement of cerebral blood flow can effectively address this pressing debate. This is the only unequivocal way to demonstrate the haemodynamic effects of rapid blood pressure reduction. The Intracerebral Haemorrhage Acutely Decreasing Arterial Pressure Trial is designed to test the hypothesis that blood pressure reduction does not result in significant or harmful changes in cerebral blood flow in acute intracerebral haemorrhage. Two hours after randomisation to a systolic blood pressure target of <150 or <180 mmHg, cerebral blood flow is measured using computed tomography perfusion, which is the primary end-point of the trial. A study of this type is critical to establishing the safety of early blood pressure treatment and is necessary for planning larger efficacy trials in a rational manner. This trial is registered with clinicaltrials.gov (NCT00963976).
The Edinburgh MouseAtlas Project (EMAP) is a time-series of mouse-embryo volumetric models. The models provide a context-free spatial framework onto which structural interpretations and experimental ...data can be mapped. This enables collation, comparison, and query of complex spatial patterns with respect to each other and with respect to known or hypothesized structure. The atlas also includes a time-dependent anatomical ontology and mapping between the ontology and the spatial models in the form of delineated anatomical regions or tissues. The models provide a natural, graphical context for browsing and visualizing complex data. The Edinburgh Mouse Atlas Gene-Expression Database (EMAGE) is one of the first applications of the EMAP framework and provides a spatially mapped gene-expression database with associated tools for data mapping, submission, and query. In this article, we describe the underlying principles of the Atlas and the gene-expression database, and provide a practical introduction to the use of the EMAP and EMAGE tools, including use of new techniques for whole body gene-expression data capture and mapping.
Nine programs were funded across eight states in the United States to customize, implement, and evaluate local campaigns in support of the national Get Yourself Tested (GYT) campaign. Each program ...promoted chlamydia screening and treatment/referral to sexually active young women (aged 15–25 years) and their partners through accessible, free, or low-cost services. This article documents the strategies and outcomes of these local GYT campaigns, highlighting the diversity in which a national sexual health campaign is implemented at the local level and identifying challenges and successes. Nearly all (n = 7) programs involved target audience members in campaign development/implementation. Youth were linked to free or low-cost sexually transmitted disease testing through community centers, high schools and colleges, community and clinic events; online or text-based ordering of test kits; and community pickup locations. Sites used a combination of traditional and new media, on-the-ground activities, promotional products, and educational and social events to promote testing. With the exception of one site, all sites reported increases in the number of persons tested for chlamydia during campaign implementation, compared to baseline. Increases ranged from 0.5% to 128%. Successes included development of local partnerships, infrastructure, and capacity; use of peer leaders and involvement; and opportunities to explore new innovations. Challenges included use of social media/new technologies, timing constraints, limited organizational and evaluation capacity, and unforeseen delays/setbacks. Each of these issues is explored, along with lessons learned, with intent to inform future sexual health promotion efforts.
Wind tunnels are used in the design and testing of a wide variety of systems and products. Wind tunnel test campaigns involve a large number of experimental data points, can take a long time to ...accomplish, and can consume tremendous resources. Design of Experiments is a systematic, statistically based approach to experimental design and analysis that has the potential to improve the efficiency and effectiveness of wind tunnel testing. In Defense Acquisition, wind tunnel testing of aircraft systems may require years of effort to fully characterize the system of interest. We employ data from a fairly large legacy wind tunnel test campaign and compare that data's corresponding response surface to the response surfaces derived from data generated using smaller, statistically motivated experimental design strategies. The comparison is accomplished using a Monte Carlo sampling methodology coupled with a statistical comparison of the system's estimated response surfaces. Initial results suggest a tremendous opportunity to reduce wind tunnel test efforts without losing test information. Published in 2010 by John Wiley & Sons, Ltd.
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