The DAGMAR Score: D-dimer assay-guided moderation of adjusted risk. Improving specificity of the D-dimer for pulmonary embolism

We generated a novel scoring system to improve the test characteristics of D-dimer in patients with suspected PE (pulmonary emboli).Electronic Medical Record data were retrospectively reviewed on Emergency Department (ED) patients 18?years or older for whom a D-dimer and imaging were ordered between June 4, 2012 and March 30, 2016. Symptoms (dyspnea, unilateral leg swelling, hemoptysis), age, vital signs, medical history (cancer, recent surgery, medications, history of deep vein thrombosis or PE, COPD, smoking), laboratory values (quantitative D-dimer, platelets, and mean platelet volume (MPV)), and imaging results (CT, VQ) were collected.Points were designated to factors that were significant in two multiple regression analyses, for PE or positive D-dimer. Points predictive of PE were designated positive values and points predictive of positive D-dimer, irrespective of presence of PE, were designated negative values.The DAGMAR (D-dimer Assay-Guided Moderation of Adjusted Risk) score was developed using age and platelet adjustment and points for factors associated with PE and elevated D-dimer.Of 8486 visits reviewed, 3523 were unique visits with imaging, yielding 2253 (26.5%) positive D-dimers. 3501 CT scans and 156 VQ scans were completed, detecting 198 PE.In our cohort, a DAGMAR Score?<?2 equated to overall PE risk?<?1.2%. Specificity improved (38% to 59%) without compromising sensitivity (94% to 96%). Use of the DAGMAR Score would have reduced CT scans from 2253 to 1556 and lead to fewer false negative results.By considering factors that affect D-dimer and also PE, we improved specificity without compromising sensitivity.     

Disseminated Blastomycosis in a Teenager Presenting with Pleural Effusion and Splenomegaly

Background

Blastomycosis is caused by a fungus endemic to states and providences bordering the Lawrence Rivers and the Great Lakes. It can lead to significant pathology in both immunocompetent and immunocompromised hosts. This case report describes disseminated blastomycosis in an otherwise healthy 16-year-old patient.

Fifty shades of graft: How to improve the efficacy of faecal microbiota transplantation for decolonization of antibiotic-resistant bacteria

Background

Spontaneous decolonization of antibiotic-resistant bacteria (ARB) takes time: approximately 25% after 30 days for carbapenem-producing Enterobacteriaceae or extended-spectrum beta-lactamase-producing Enterobacteriaceae. Faecal microbiota transplantation (FMT) has been proposed as a new strategy to promote decolonization in order to reduce the risk of superinfection due to these ARB. This paper discusses the literature on the use of FMT for this indication, and the improvement levers available to promote its efficacy.

Laser‐based radiocarbon detection in the laboratory: How soon?

Research over the past 25 years and the use of accelerator mass spectrometry (AMS) have demonstrated benefits of single‐atom counting of ¹⁴C compared with scintillation monitoring of ¹⁴C radioactive decay for a multitude of applications in drug development studies. These include pharmacokinetics and metabolism studies, microdosing studies, and quantification of DNA adducts. In the last decade, the possibility of single‐atom counting using lasers has been demonstrated, providing the possibility of simplified laboratory‐based systems, which can equal or excel AMS sensitivity and provide scintillation system convenience without high levels of radioactivity. To achieve the required sensitivity, optical storage cavities have been used to enhance the laser interaction of the low densities of radiocarbon present. Two types of laser technologies have been used‐cavity ring‐down spectroscopy (CRDS) and intracavity opto‐galvanic spectroscopy (ICOGS). Problems to be overcome to achieve routine use have included separation of the ¹⁴C signal from backgrounds, achievement of acceptable precision and accuracy, reduction of measurement times for small samples, and improvement in the ease of use for the operator. Both technologies have achieved impressive results to date using samples of order 1 mg with CRDS and 10 μg with ICOGS. Commercial development is the next step.     

Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.