Development of the Surgical Patient safety Observation Tool (SPOT)

Background: A Surgical Patient safety Observation Tool (SPOT) was developed and tested in a multicentre observational pilot study. The tool enables monitoring and benchmarking perioperative safety performance across departments and hospitals, covering international patient safety goals. Methods: Nineteen perioperative patient safety observation topics were selected from Dutch perioperative patient safety guidelines, which also cover international patient safety goals. All items that measured these selected topics were then extracted from available local observation checklists of the participating hospitals. Experts individually prioritized the best measurement items per topic in an initial written Delphi round. The second (face to face) Delphi round resulted in consensus on the content of SPOT, after which the measurable elements (MEs) per topic were defined. Finally, the tool was piloted in eight hospitals for measurability, applicability, improvement potential, discriminatory capacity and feasibility. Results: The pilot test showed good measurability for all 19 patient safety topics (range of 8-291 MEs among topics), with good applicability (median 97 (range 11.8-100) per cent). The overall improvement potential appeared to be good (median 89 (range 72.5-100) per cent), and at topic level the tool showed good discriminatory capacity (variation 27.5 per cent, range in compliance 72.5-100 per cent). Overall scores showed relatively little variation between the participating hospitals (variation 13 per cent, range in compliance 83-96 per cent). All eight auditors considered SPOT a straightforward and easy-to-use tracer tool. Conclusion: A comprehensive tool to measure safety of care was developed and validated using a systematic, stepwise method, enabling hospitals to monitor, benchmark and improve perioperative safety performance

Joint Activity and Attenuation Reconstruction From Multiple Energy Window Data With Photopeak Scatter Re-Estimation in Non-TOF 3-D PET

Estimation of attenuation from positron emission tomography (PET) data only is of interest for hybrid PET-MR and systems where CT is not available or recommended. However, when using data from a single energy window, emission-based non-time-of-flight (TOF) PET attenuation correction (AC) methods suffer from “cross-talk” artifacts. Based on earlier work, this article explores the hypothesis that cross-talk can be reduced by using more than one energy window. We propose an algorithm for the simultaneous estimation of both activity and attenuation images, as well as, the scatter component of the measured data from a PET acquisition, using multiple energy windows. The model for the measurements is 3-D and accounts for the finite energy resolution of PET detectors; it is restricted to single scatter. The proposed energy-based simultaneous maximum likelihood reconstruction of activity and attenuation with photopeak scatter re-estimation algorithm is compared with simultaneous estimation from a single energy window simultaneous maximum likelihood reconstruction of activity and attenuation with photopeak scatter re-estimation. The evaluation is based on simulations using the characteristics of the Siemens mMR scanner. Phantoms of different complexity were investigated. In particular, a 3-D XCAT torso phantom was used to assess the inpainting of attenuation values within the lung region. Results show that the cross-talk present in non-TOF maximum likelihood reconstruction of activity and attenuation reconstructions is significantly reduced when using multiple energy windows and indicate that the proposed approach warrants further investigation

Joint Activity and Attenuation Reconstruction from Multiple Energy Window Data with Photopeak Scatter Re-Estimation in non-TOF 3D PET

Estimation of attenuation from PET data only is of interest for PET-MR and systems where CT is not available or recommended. However, when using data from a single energy window, emission-based non-TOF PET AC methods suffer from ‘cross-talk’ artefacts. Based on earlier work, this manuscript explores the hypothesis that cross-talk can be reduced by using more than one energy window. We propose an algorithm for the simultaneous estimation of both activity and attenuation images as well as the scatter component of the measured data from a PET acquisition, using multiple energy windows. The model for the measurements is 3D and accounts for the finite energy resolution of PET detectors; it is restricted to single scatter. The proposed MLAA-EB-S algorithm is compared with simultaneous estimation from a single energy window (MLAA-S). The evaluation is based on simulations using the characteristics of the Siemens mMR scanner. Phantoms of different complexity were investigated. In particular, a 3D XCAT torso phantom was used to assess the inpainting of attenuation values within the lung region. Results show that the cross-talk present in non-TOF MLAA reconstructions is significantly reduced when using multiple energy windows and indicate that the proposed approach warrants further investigation

TLR4 genetic variation is associated with inflammatory responses in Gram-positive sepsis.

OBJECTIVES: To identify important pathogen recognition receptor (PRR) pathways regulating innate immune responses and outcome in Staphylococcus aureus sepsis. METHODS: We analysed whether candidate PRR pathway genetic variants were associated with killed S. aureus-induced cytokine responses ex vivo and performed follow-up in vitro studies. We tested the association of our top-ranked variant with cytokine responses and clinical outcomes in a prospective multicentre cohort of patients with staphylococcal sepsis. RESULTS: An intronic TLR4 polymorphism and expression quantitative trait locus, rs1927907, was highly associated with cytokine release induced by stimulation of blood from healthy Thai subjects with S. aureus ex vivo. S. aureus did not induce TLR4-dependent NF-κB activation in transfected HEK293 cells. In monocytes, tumor necrosis factor (TNF)-α release induced by S. aureus was not blunted by a TLR4/MD-2 neutralizing antibody, but in a monocyte cell line, TNF-α was reduced by knockdown of TLR4. In Thai patients with staphylococcal sepsis, rs1927907 was associated with higher interleukin (IL)-6 and IL-8 levels as well as with respiratory failure. S. aureus-induced responses in blood were most highly correlated with responses to Gram-negative stimulants whole blood. CONCLUSIONS: A genetic variant in TLR4 is associated with cytokine responses to S. aureus ex vivo and plasma cytokine levels and respiratory failure in staphylococcal sepsis. While S. aureus does not express lipopolysaccharide or activate TLR4 directly, the innate immune response to S. aureus does appear to be modulated by TLR4 and shares significant commonality with that induced by Gram-negative pathogens and lipopolysaccharide

Metabolomics Study of Urine in Autism Spectrum Disorders Using a Multiplatform Analytical Methodology

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with no clinical biomarker. Aims of this study were to characterize a metabolic signature of ASD, and to evaluate multi-platform analytical methodologies in order to develop predictive tools for diagnosis and disease follow up. Urines were analyzed using: 1H- and 1 H-13C-NMR-based approaches and LC-HRMS-based approaches (ESI+ and ESI- on a HILIC and C18 chromatography column). Data tables obtained from the six analytical modalities on a training set of 46 urines (22 autistic children and 24 controls) were processed by multivariate analysis (OPLS-DA). Prediction of each of these OPLS-DA models were then evaluated using a prediction set of 16 samples (8 autistic children and 8 controls) and ROC curves. Thereafter, a data fusion block-scaling OPLS-DA model was generated from the 6 best models obtained for each modality. This fused OPLSDA model showed an enhanced performance (R 2Y(cum)=0.88, Q 2 (cum)=0.75) compared to each analytical modality model, as well as a better predictive capacity (AUC=0.91, p-value 0.006). Metabolites that are most significantly different between autistic and control children (p<0.05) are indoxyl sulfate, N-\u2329-Acetyl-L-arginine, methyl guanidine and phenylacetylglutamine. This multi-modality approach has the potential to contribute to find robust biomarkers and characterize a metabolic phenotype of the ASD population

Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

Improved Siderotic Nodule Detection in Cirrhosis with Susceptibility-Weighted Magnetic Resonance Imaging: A Prospective Study

BACKGROUND: Hepatic cirrhosis is a common pathway of progressive liver destruction from multiple causes. Iron uptake can occur within the hepatic parenchyma or within the various nodules that form in a cirrhotic liver, termed siderotic nodules. Siderotic nodule formation has been shown to correlate with inflammatory activity, and while the relationship between siderotic nodule formation and malignancy remains unclear, iron distribution within hepatic nodules has known implications for the detection of hepatocellular carcinoma. We aimed to evaluate the role of abdominal susceptibility-weighted imaging in the detection of siderotic nodules in cirrhotic patients. METHODOLOGY/PRINCIPAL FINDINGS: Forty-six (46) cirrhotic patients with at least one siderotic nodule detected on previous imaging underwent both computed tomography and magnetic resonance imaging (T1-, T2-, T2*-, and susceptibility-weighted imaging) at 3.0 Tesla. Imaging data was independently analyzed by two radiologists. Siderotic nodule count was determined for each modality and imaging sequence. For each magnetic resonance imaging technique, siderotic nodule conspicuity was assessed on a 3 point scale (1 = weak, 2 = moderate, 3 = strong). More nodules were detected by susceptibility weighted imaging (n = 2935) than any other technique, and significantly more than by T2* weighted imaging (n = 1696, p<0.0001). Lesion conspicuity was also highest with susceptibility-weighted imaging, with all nodules found to be moderate (n = 6) or strong (n = 40); a statistically significant difference (p<0.001). CONCLUSIONS: Susceptibility-weighted imaging had the greatest lesion conspicuity and detected the highest number of siderotic nodules suggesting it is the most sensitive imaging technique to detect siderotic nodules in cirrhotic patients