Deep learning-based segmentation of malignant pleural mesothelioma tumor on computed tomography scans: application to scans demonstrating pleural effusion

Tumor volume is a topic of interest for the prognostic assessment, treatment response evaluation, and staging of malignant pleural mesothelioma. Many mesothelioma patients present with, or develop, pleural fluid, which may complicate the segmentation of this disease. Deep convolutional neural networks (CNNs) of the two-dimensional U-Net architecture were trained for segmentation of tumor in the left and right hemithoraces, with the networks initialized through layers pretrained on ImageNet. Networks were trained on a dataset of 5230 axial sections from 154 CT scans of 126 mesothelioma patients. A test set of 94 CT sections from 34 patients, who all presented with both tumor and pleural effusion, in addition to a more general test set of 130 CT sections from 43 patients, were used to evaluate segmentation performance of the deep CNNs. The Dice similarity coefficient (DSC), average Hausdorff distance, and bias in predicted tumor area were calculated through comparisons with radiologist-provided tumor segmentations on the test sets. The present method achieved a median DSC of 0.690 on the tumor and effusion test set and achieved significantly higher performance on both test sets when compared with a previous deep learning-based segmentation method for mesothelioma

Do knowledge infrastructure facilities support Evidence-Based Practice in occupational health? An exploratory study across countries among occupational physicians enrolled on Evidence-Based Medicine courses

<p>Abstract</p> <p>Background</p> <p>Evidence-Based Medicine (EBM) is an important method used by occupational physicians (OPs) to deliver high quality health care. The presence and quality of a knowledge infrastructure is thought to influence the practice of EBM in occupational health care. This study explores the facilities in the knowledge infrastructure being used by OPs in different countries, and their perceived importance for EBM practice.</p> <p>Methods</p> <p>Thirty-six OPs from ten countries, planning to attend an EBM course and to a large extent recruited via the European Association of Schools of Occupational Medicine (EASOM), participated in a cross-sectional study.</p> <p>Results</p> <p>Research and development institutes, and knowledge products and tools are used by respectively more than 72% and more than 80% of the OPs and they are rated as being important for EBM practice (more than 65 points (range 0–100)). Conventional knowledge access facilities, like traditional libraries, are used often (69%) but are rated as less important (46.8 points (range 0–100)) compared to the use of more novel facilities, like question-and-answer facilities (25%) that are rated as more important (48.9 points (range 0–100)). To solve cases, OPs mostly use non evidence-based sources. However, they regard the evidence-based sources that are not often used, e.g. the Cochrane library, as important enablers for practising EBM. The main barriers are lack of time, payment for full-text articles, language barrier (most texts are in English), and lack of skills and support.</p> <p>Conclusion</p> <p>This first exploratory study shows that OPs use many knowledge infrastructure facilities and rate them as being important for their EBM practice. However, they are not used to use evidence-based sources in their practice and face many barriers that are comparable to the barriers physicians face in primary health care.</p

QTc and psychopharmacs: are there any differences between monotherapy and polytherapy

<p>Abstract</p> <p>Background</p> <p>Some psychotropic drugs are connected with prolongation of QT interval, increased risk of cardiac arrhythmias and greater incidence of sudden death, especially when used in combination. Concomitant use of antipsychotics and antidepressants is not rare in our clinical practice. The study compares the length of QT interval in patients on monotherapy with an antipsychotic or an antidepressant and patients taking polytherapy (an antipsychotic agent combined with an antidepressant).</p> <p>Methods</p> <p>Sixty-one hospitalized women who met the ICD-10 criteria for schizophrenia, schizoaffective psychosis, delusional disorder and mood disorder were included in the study. The monotherapy group was consisted of thirty-two women treated with an antipsychotic or an antidepressant while the polytherapy group was composed of twenty-nine women treated with an antipsychotic agent plus an antidepressant. Two electrocardiograms (ECGs) were obtained for each patient: the first was carried out before the treatment and the second after two weeks of treatment.</p> <p>Statistical analysis was carried out by SPSS program and included unpaired and paired t test and Fisher's exact test.</p> <p>Results</p> <p>Mean baseline QTc values did not differ between the groups (439 ± 22 ms was the same value found in the both groups; unpaired t test, p > 0.5). Mean QTc intervals after two weeks of treatment were also similar (439 ± 24 ms in the monotherapy group and 440 ± 20 ms in the polytherapy group; unpaired t test, p > 0.5). Fisher's exact test did not reveal significant difference in the number of patients with borderline (451–470 ms) or prolonged (> 470 ms) QTc between groups, neither before treatment nor after two weeks of treatment. Twenty two women of the total of sixty one patients (36%) had QTc > 450 ms before applying therapy.</p> <p>Conclusion</p> <p>We did not find significant QT prolongation in our patients after two weeks of treatment with antipsychotics and/or antidepressants. The QTc interval length did not differ significantly in the monotherapy and the polytherapy group. More than one third of included women exceeded the threshold value of borderline QTc interval (450 ms) before starting treatment. This finding calls for caution when prescribing drugs to female psychiatric patients, especially if they have other health problems.</p

Evaluation of a clinical decision support tool for osteoporosis disease management: protocol for an interrupted time series design

<p>Abstract</p> <p>Background</p> <p>Osteoporosis affects over 200 million people worldwide at a high cost to healthcare systems. Although guidelines on assessing and managing osteoporosis are available, many patients are not receiving appropriate diagnostic testing or treatment. Findings from a systematic review of osteoporosis interventions, a series of mixed-methods studies, and advice from experts in osteoporosis and human-factors engineering were used collectively to develop a multicomponent tool (targeted to family physicians and patients at risk for osteoporosis) that may support clinical decision making in osteoporosis disease management at the point of care.</p> <p>Methods</p> <p>A three-phased approach will be used to evaluate the osteoporosis tool. In phase 1, the tool will be implemented in three family practices. It will involve ensuring optimal functioning of the tool while minimizing disruption to usual practice. In phase 2, the tool will be pilot tested in a quasi-experimental interrupted time series (ITS) design to determine if it can improve osteoporosis disease management at the point of care. Phase 3 will involve conducting a qualitative postintervention follow-up study to better understand participants' experiences and perceived utility of the tool and readiness to adopt the tool at the point of care.</p> <p>Discussion</p> <p>The osteoporosis tool has the potential to make several contributions to the development and evaluation of complex, chronic disease interventions, such as the inclusion of an implementation strategy prior to conducting an evaluation study. Anticipated benefits of the tool may be to increase awareness for patients about osteoporosis and its associated risks and provide an opportunity to discuss a management plan with their physician, which may all facilitate patient self-management.</p

15-Deoxy-Δ12,14 Prostaglandin J2 Reduces the Formation of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice

AIM: 15-deoxy-Δ¹²,¹⁴ prostaglandin J₂ (15d-PGJ₂) is a ligand of peroxisome proliferator-activated receptor γ (PPARγ) having diverse effects such as the differentiation of adipocytes and atherosclerotic lesion formation. 15d-PGJ₂ can also regulate the expression of inflammatory mediators on immune cells independent of PPARγ. We investigated the antiatherogenic effect of 15d-PGJ₂. METHODS: We fed apolipoprotein (apo) E-deficient female mice a Western-type diet from 8 to 16 wk of age and administered 1 mg/kg/day 15d-PGJ₂ intraperitoneally. We measured atherosclerotic lesions at the aortic root, and examined the expression of macrophage and inflammatory atherosclerotic molecules by immunohistochemical and real-time PCR in the lesion. RESULTS: Atherosclerotic lesion formation was reduced in apo E-null mice treated with 15d-PGJ₂, as compared to in the controls. Immunohistochemical and real-time PCR analyses showed that the expression of MCP-1, TNF-α, and MMP-9 in atherosclerotic lesions was significantly decreased in 15d-PGJ₂ treated mice. The 15d-PGJ₂ also reduced the expression of macrophages and RelA mRNA in atherosclerotic lesions. CONCLUSION: This is the first report 15d-PGJ₂, a natural PPARγ agonist, can improve atherosclerotic lesions in vivo. 15d-PGJ₂ may be a beneficial therapeutic agent for atherosclerosis

Abrogation of IL-6-mediated JAK signalling by the cyclopentenone prostaglandin 15d-PGJ2 in oral squamous carcinoma cells

Cyclopentenone 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) exerts antineoplastic effects on various types of human cancer. We recently showed that treatment with 15d-PGJ2 induces apoptosis accompanied by downregulation of the oncogenic signal transducer and activator of transcription 3 (Stat3) signalling in human oral squamous cell carcinoma (SCC) cells. The current study examines the effects of 15d-PGJ2 on the epidermal growth factor receptor (EGFR) and Janus Kinase (JAK)-mediated signalling pathways. Inhibition of Stat3 by 15d-PGJ2 was abolished by exogenous stimulation with transforming growth factor alpha (TGF-α), but not interleukin 6 (IL-6), supporting a selective effect of 15d-PGJ2 on IL-6-mediated signalling. Importantly, 15d-PGJ2 selectively abrogated constitutive and IL-6-mediated JAK phosphorylation without affecting EGFR-activated levels. Moreover, the inhibitory effect of 15d-PGJ2 on JAK signalling required the reactive α,β-unsaturated carbon within the cyclopentenone ring. Targeting of JAK signalling using a specific JAK inhibitor also abolished Stat3 phosphorylation and resulted in apoptosis in oral SCC cells. Our findings provide the first evidence for 15d-PGJ2–mediated downregulation of constitutive and IL-6-induced JAK signalling in cancer and support that JAK inhibition and suppression of EGFR-independent Stat3 activation by 15d-PGJ2 represent a promising approach for induction of apoptosis in oral SCC cells

Activation of transcription factors by extracellular nucleotides in immune and related cell types

Extracellular nucleotides, acting through P2 receptors, can regulate gene expression via intracellular signaling pathways that control the activity of transcription factors. Relatively little is known about the activation of transcription factors by nucleotides in immune cells. The NF-κB family of transcription factors is critical for many immune and inflammatory responses. Nucleotides released from damaged or stressed cells can act alone through certain P2 receptors to alter NF-κB activity or they can enhance responses induced by pathogen-associated molecules such as LPS. Nucleotides have also been shown to regulate the activity of other transcription factors (AP-1, NFAT, CREB and STAT) in immune and related cell types. Here, we provide an overview of transcription factors shown to be activated by nucleotides in immune cells, and describe what is known about their mechanisms of activation and potential functions. Furthermore, we propose areas for future work in this new and expanding field