Physician choices in pulmonary embolism testing

BACKGROUND:Evidence-based guidelines advise excluding pulmonary embolism (PE) diagnosis using d-dimer in patients with a lower probability of PE. Emergency physicians frequently order computed tomography (CT) pulmonary angiography without d-dimer testing or when d-dimer is negative, which exposes patients to more risk than benefit. Our objective was to develop a conceptual framework explaining emergency physicians’ test choices for PE.METHODS:We conducted a qualitative study using in-depth interviews of emergency physicians in Canada. A nonmedical researcher conducted in-person interviews. Participants described how they would test simulated patients with symptoms of possible PE, answered a knowledge test and were interviewed on barriers to using evidence-based PE tests.RESULTS:We interviewed 63 emergency physicians from 9 hospitals in 5 cities, across 3 provinces. We identified 8 domains: anxiety with PE, barriers to using the evidence (time, knowledge and patient), divergent views on evidence-based PE testing, inherent Wells score problems, the drive to obtain CT rather than to diagnose PE, gestalt estimation artificially inflating PE probability, subjective reasoning and cognitive biases supporting deviation from evidence-based tests and use of evidence-based testing to rule out PE in patients who are very unlikely to have PE. Choices for PE testing were influenced by the disease, environment, test qualities, physician and probability of PE.INTERPRETATION:Analysis of structured interviews with emergency physicians provided a conceptual framework to explain how these physicians use tests for suspected PE. The data suggest 8 domains to address when implementing an evidence-based protocol to investigate PE.

Pulmonary embolism (PE) occurs when a blood clot lodges in the pulmonary arteries. If left untreated, the disorder can progress, causing worsening morbidity and may become fatal.¹ Because of the acute nature of this condition, many patients with PE present to the emergency department.Diagnosing and excluding PE using computed tomography pulmonary angiography (CTPA) alone can be problematic because of radiation exposure, anaphylaxis to contrast, misdiagnosis and “overdiagnosis” of inconsequential PE² (leading to unnecessary anticoagulation therapy and psychological distress³). Choosing Wisely^4,5 and the guideline from the American College of Physicians⁶ recommend the use of risk stratification tools, including the Pulmonary Embolism Rule-out Criteria (PERC) clinical decision rule,⁷ the Wells score⁸ and blood concentration of d-dimer. These tools use different predetermined diagnostic algorithms to indicate the need for CTPA.^8–11 Evidence-based guidelines discourage further testing in patients at lower risk who have normal d-dimer levels, where imaging can cause more harm than benefit.^12,13 However, many emergency physicians opt for CTPA as a stand-alone test for PE.^14–17It remains unclear why emergency physicians sometimes do not use validated diagnostic PE tools. Furthermore, implementation of computerized decision support systems has had little success in modifying this behaviour.^18,19 We sought to develop a conceptual framework to describe how Canadian emergency physicians test for PE, and to document the cognitive and contextual barriers to using existing evidence-based diagnostic PE pathways.     

Development of novel isatin–nicotinohydrazide hybrids with potent activity against susceptible/resistant Mycobacterium tuberculosis and bronchitis causing–bacteria

Joining the global fight against Tuberculosis, the world''s most deadly infectious disease, herein we present the design and synthesis of novel isatin-nicotinohydrazide hybrids (5a–m and 9a–c) as promising anti-tubercular and antibacterial agents. The anti-tubercular activity of the target hybrids was evaluated against drug-susceptible M. tuberculosis strain (ATCC 27294) where hybrids 5d, 5g and 5h were found to be as potent as INH with MIC = 0.24 µg/mL, also the activity was evaluated against Isoniazid/Streptomycin resistant M. tuberculosis (ATCC 35823) where compounds 5g and 5h showed excellent activity (MIC = 3.9 µg/mL). Moreover, the target hybrids were examined against six bronchitis causing-bacteria. Most derivatives exhibited excellent antibacterial activity. K. pneumonia emerged as the most sensitive strain with MIC range: 0.49–7.81 µg/mL. Furthermore, a molecular docking study has proposed DprE1 as a probable enzymatic target for herein reported isatin-nicotinohydrazide hybrids, and explored the binding interactions within the vicinity of DprE1 active site.     

Adherence ofStaphylococcus epidermidis to pharyngeal epithelial cells mediated by lipoteichoic acid

Prior treatment of pharyngeal epithelial cells (PEC) with lipoteichoic acid (LTA) derived fromStaphylococcus epidermidis produced a marked inhibition of adherence of the homologous strain and two heterologous strains. The inhibition was dose dependent and saturable with 100 µg/ml of LTA. However, pretreatment of PEC with deacylated LTA did not block the adherence of the three strains tested. A similar but less marked blocking effect on the adherence ofS. epidermidis to PEC was also observed with LTAs derived fromS. aureus andStreptococcus pyogenes. On treatment of bacteria with substances capable of binding to LTA, such as polyclonal mouse anti-LTA antibodies or with human albumin, a marked inhibition of bacterial adherence was observed. Immunofluorescence studies showed that anti-LTA antiserum bound readily to the surface of bacterial cells. These findings provide clear evidence that the lipid component of LTA located on the bacterial surface is centrally involved in the adherence ofS. epidermidis to human mucosal cells.     

Regulatory effect of diosgenin on lipogenic genes expression in high-fat diet-induced obesity in mice

Obesity is one of the most serious health problems in the world, increasing the risk of other chronic diseases. Alterations in fatty acid synthesis related genes are crucially involved in obesity progression. Diosgenin (DG) was one of the phytosterols compounds with vital activity against lipid disorders. Therefore, this study was intended to evaluate the protective effect of DG on lipogenesis in the high-fat diet (HFD)-induced obesity in mice, via investigating the expression of two of the fatty acid synthesis–involved genes; sterol regulatory element-binding protein (SREBP-1c) and fatty acid synthase (FASN) genes. Thirty adult male mice were divided into 3 groups. Control group, fed with normal diet; HFD group, mice fed with a high-fat diet and HFD + DG group, mice fed with a high-fat diet and supplemented in parallel with DG for 6 consecutive weeks. The effect of DG on Body weights, liver enzymes, lipid profile, were evaluated. Histopathological fatty changes as well as SREBP-1c and FASN gene expression were also investigated. DG significantly alleviated body weight gain, adjusted liver enzymes, and improved lipid profile. Additionally, DG ameliorated the histopathological changes by reducing the lipid vacuoles and hence the hepatosteatosis. Accordingly, DG significantly downregulated the two-fold increase in the SREBP-1c and FASN gene expression observed in the HFD group. In conclusion, DG possesses a beneficial impact against diet-induced obesity in mice, which makes it a good candidate for NAFLD and obesity prevention.