Krogsgaardhorowitz3071

Background Transfusion-dependent haemoglobinopathies require lifelong iron chelation therapy with one of the three iron chelators (deferiprone, deferasirox, or deferoxamine). Deferasirox and deferiprone are the only two oral chelators used in adult patients with transfusion-dependent haemoglobinopathies. To our knowledge, there are no randomised clinical trials comparing deferiprone, a less expensive iron chelator, with deferasirox in paediatric patients. We aimed to show the non-inferiority of deferiprone versus deferasirox. Methods DEEP-2 was a phase 3, multicentre, randomised trial in paediatric patients (aged 1 month to 18 years) with transfusion-dependent haemoglobinopathies. The study was done in 21 research hospitals and universities in Italy, Egypt, Greece, Albania, Cyprus, Tunisia, and the UK. PI3K inhibitor Participants were receiving at least 150 mL/kg per year of red blood cells for the past 2 years at the time of enrolment, and were receiving deferoxamine (10 years) to show non-inferiority of deferiprone versussafe in inducing control of iron overload during 12 months of treatment. Considering the need for availability of more chelation treatments in paediatric populations, deferiprone offers a valuable treatment option for this age group. Funding EU Seventh Framework Programme.Background Daratumumab showed encouraging efficacy as monotherapy in patients with heavily pretreated multiple myeloma in the GEN501 and SIRIUS studies. Here we report a pooled, post-hoc final analysis of these two studies. Methods GEN501 was an open-label, multicentre, phase 1-2, dose escalation and expansion study done in the Netherlands, the USA, Sweden, and Denmark. Eligible patients had multiple myeloma and had relapsed or were refractory to 2 or more previous lines of treatment that included a proteasome inhibitor or an immunomodulatory drug. SIRIUS was an open-label, multicentre, phase 2 study done in Canada, Spain, and the USA, in which eligible patients with multiple myeloma had received 3 or more previous lines of therapy, including a proteasome inhibitor or an immunomodulatory drug, or were double refractory. In both studies, eligible patients were aged 18 years or older and had an Eastern Cooperative Oncology Group performance status of 2 or less. In part 2 of GEN501, patients were given intravenoluding 20 (14%) of 148 patients with very good partial response or better (8·5-20·1) and seven (5%) patients reporting complete response or better (1·9-9·5). Among 45 responders, the median duration of response was 8·0 months (95% CI 6·5-14·7). Median overall survival was 20·5 months (95% CI 16·6-28·1), with a 3-year overall survival rate of 36·5% (28·4-44·6). The most common grade 3-4 treatment-emergent adverse events (TEAEs) were anaemia (grade 3, 26 [18%] of 148 patients; no grade 4 events) and thrombocytopenia (grade 3, 13 [9%] of 148 patients; grade 4, 8 [5%] of 148 patients). Serious drug-related TEAEs occurred in 13 (9%) of 148 patients. There were no treatment-related deaths. Interpretation In this analysis, daratumumab 16 mg/kg monotherapy showed durable responses and there were no new safety concerns with longer follow-up. Funding Janssen Research & Development.The ASGE's GIE Editorial Board reviewed original endoscopy-related articles published during 2019 in GIE and 10 other leading medical and gastroenterology journals. Votes from each individual member were tallied to identify a consensus list of 10 topic areas of major advances in GI endoscopy. Individual board members summarized important findings published in these 10 areas of disinfection, artificial intelligence, bariatric endoscopy, adenoma detection, polypectomy, novel imaging, Barrett's esophagus, third space endoscopy, interventional EUS, and training. This document summarizes these "Top 10" endoscopic advances of 2019.Background and aims Magnetically controlled capsule endoscopy (MCE) has become an efficient diagnostic modality for gastric diseases. We developed a novel automatic gastric lesion detection system to assist in diagnosis and reduce inter-physician variations. This study aimed to evaluate the diagnostic capability of the computer-aided detection system for MCE images. Methods We developed a novel automatic gastric lesion detection system based on convolutional neural network (CNN) and faster region-based convolutional neural network (Faster-RCNN). A total of 1,023,955 MCE images from 797 patients were enrolled to train and test the system. These images were divided into 7 categories (erosion, polyp, ulcer, submucosal tumor, xanthoma, normal mucosa, and invalid images). The primary endpoint was the sensitivity of the system. Results The system detected gastric focal lesions with 96.2% sensitivity (95% confidence interval (CI), 95.7%-96.5%), 76.2% specificity (95% CI, 75.97%-76.3%), 16.0% positive predictive value (95% CI, 15.7%-16.3%), 99.7% negative predictive value (95% CI, 99.74%-99.79%), and 77.1% accuracy (95% CI, 76.9%-77.3%) (sensitivity was 99.3% for erosions; 96.5% for polyps; 89.3% for ulcers; 87.2% for submucosal tumors; 90.6% for xanthomas; 67.8% for normal; and 96.1% for invalid images). On ROC curve analysis, the area under the curve for all positive images was 0.84. Image processing time was 44 milliseconds per image for the system and 0.38±0.29 seconds per image for clinicians (P＜0.001). The kappa value of 2 times repeated read was 1. Conclusions The CNN Faster-RCNN-based diagnostic program system showed good performance in diagnosing gastric focal lesions in MCE images.In a world with an ageing population, dementia has become an urgent threat to global health and wellbeing. Psychosocial and lifestyle factors, such as higher socioeconomic positions, longer times spent in education, greater occupational complexity, reduced stress at work, and engagement in mental, physical, and social activities, have been hypothesised to supply resilience against dementia. Although questions remain surrounding the role of these factors in the development of dementia, scientific advancements have considerably expanded our understanding of modifiable psychosocial and lifestyle factors and their neuroprotective and compensatory influences over a life course. Evidence from observational studies is robust enough to suggest that stimulating psychosocial and lifestyle factors are protective against dementia. And, although the corresponding evidence from intervention studies is still scarce, public health campaigns promoting psychosocial and lifestyle factors might improve the health and wellbeing of people aged 60 years and older.