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ANLN truncation causes a familial fatal acute respiratory distress syndrome in Dalmatian dogs
No full textDevelopment of a Blocking ELISA Using a Monoclonal Antibody to a Dominant Epitope in Non-Structural Protein 3A of Foot-and-Mouth Disease Virus, as a Matching Test for a Negative-Marker Vaccine
No full textDefining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria
No full textClinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria.Three datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African ‘AQUAMAT’ trial comparing artesunate and quinine (children), and the Vietnamese ‘AQ’ study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortality explained (PTE) by these surrogate measures.Improvements in lactate concentration or coma scores over the first 24 hours of admission, were strongly prognostic for survival in all datasets. In hyperlactataemic patients in the AQ study (n = 173), lower mortality with artemether compared to quinine closely correlated with faster reduction in plasma lactate concentration, with a high PTE of the relative change in plasma lactate at 8 and 12 hours of 0.81 and 0.75, respectively. In paediatric patients enrolled in the ‘AQUAMAT’ study with cerebral malaria (n = 785), mortality was lower with artesunate compared to quinine, but this was not associated with faster coma recovery.The relative changes in plasma lactate concentration assessed at 8 or 12 hours after admission are valid surrogate endpoints for severe malaria studies on antimalarial drugs or adjuvant treatments aiming at improving the microcirculation. Measures of coma recovery are not valid surrogate endpoints for mortality
High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients
No full textWe searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis.We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF.When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms.Our results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis
genetic polymorphism and cigarette smoking on the clinicopathologic development of hepatocellular carcinoma
No full text genetic variants play a role in hepatocellular carcinoma (HCC) susceptibility remains unknown. thrombospondin type 1 repeat and a novel proline-rich region embedded within the C-terminal extension, respectively. gene polymorphism as a predict factor during the progression of HCC
The Association between Foveal Morphology and Macular Pigment Spatial Distribution: An Ethnicity Study
No full textMacular pigment (MP) spatial distribution varies considerably among individuals. We investigated ethnic variations in MP spatial distribution in relation to foveal architecture.We measured MP optical density (MPOD) using heterochromatic flicker photometry (MAP test, City, University of London) in 76 white, 80 South Asian and 70 black volunteers (18 to 39 years). MPOD spatial profiles were classified objectively as exponential, ring-like or central dip, based on deviations away from an exponential fit. Measurements including total retinal thickness (RT), inner retinal layer (IRL), inner and outer plexiform layer (IPL and OPL) thickness, foveal width and foveal pit slope were taken from Spectralis SD-OCT (Heidelberg, Germany) scans.(4,226) = 13.4, P = 0.009). MPODint was lower in exponential (0.66±0.21) compared to ring-like (0.96±0.26) and central dip (1.00±0.32, P<0.0005) groups. White subjects had thicker IRL at 0° (130±21μm) than South Asian (123±16μm) and blacks (116±14μm; F(2) = 12.4, P<0.0005), with comparable results for IPL (P<0.0005) and OPL (P = 0.03). There was no significant difference in IRL, IPL or OPL (from 0 to 3.8° retinal eccentricity) or foveal width between MP profile groups (P>0.05).We report a significant difference in the amount and distribution of MP between ethnicities that is not explained by variations in foveal morphology
The association between frequent alcohol drinking and opioid consumption after abdominal surgery: A retrospective analysis
No full textIt is perceived that patients with a history of frequent alcohol consumption require more opioids for postoperative pain control and experience less postoperative nausea and vomiting than patients without such a history. However, there is scarce evidence supporting this notion. The aim of this study was to assess association between frequent alcohol consumption and opioid requirement for postoperative pain control and occurrence of postoperative nausea and vomiting.The medical records for 4143 patients using intravenous patient-control analgesia with opioids after abdominal surgery between January 2010 and September 2013 were obtained, and associations were sought between the cumulative opioid consumption (in intravenous morphine equivalence) per body weight (mg/kg) in the first 2 days after abdominal operation and several demographic and clinical variables by multiple regression analysis. The association between the occurrence of postoperative nausea and vomiting and several demographic and clinical variables was also sought by multiple logistic regression analysis. = 0.026).Frequent alcohol drinking was associated with increased opioid consumption for postoperative pain control and decreased risks of postoperative nausea and vomiting after abdominal surgery