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© 2017 Ferrata Storti Foundation. Primary immune thrombocytopenia is an autoimmune disorder characterized by increased platelet destruction and insufficient platelet production without another identified underlying disorder. Splenectomy may alter responsiveness to treatment and/or increase the risk of thrombosis, infection, and pulmonary hypertension. The analysis herein evaluated the safety and efficacy of the thrombopoietin receptor agonist romiplostim in splenectomized and nonsplenectomized adults with primary immune thrombocytopenia. Data were pooled across 13 completed clinical studies in adults with immune thrombocytopenia from 2002-2014. Adverse event rates were adjusted for time of exposure. Results were considered different when 95% confidence intervals were non-overlapping. Safety was analyzed for 1111 patients (395 splenectomized; 716 nonsplenectomized) who received romiplostim or control (placebo or standard of care). At baseline, splenectomized patients had a longer median duration of immune thrombocytopenia and a lower median platelet count, as well as a higher proportion with >3 prior immune thrombocytopenia treatments versus nonsplenectomized patients. In each treatment group, splenectomized patients used rescue medications more often than nonsplenectomized patients. Platelet response rates (≥50×109/L) for romiplostim were 82% (310/376) for splenectomized and 91% (592/648) for nonsplenectomized patients (P<0.001 by Cochran-Mantel-Haenszel test). Platelet responses were stable over time in both subgroups. Exposure-adjusted adverse event rates were higher for control versus romiplostim for both splenectomized (1857 versus 1226 per 100 patient-years) and nonsplenectomized patients (1052 versus 852 per 100 patient-years). In conclusion, responses to romiplostim were seen in both splenectomized and nonsplenectomized patients, and romiplostim was not associated with an increase in the risk of adverse events in splenectomized patients. clinical-trials.gov I

© 2017 Ferrata Storti Foundation. Primary immune thrombocytopenia is an autoimmune disorder characterized by increased platelet destruction and insufficient platelet production without another identified underlying disorder. Splenectomy may alter responsiveness to treatment and/or increase the risk of thrombosis, infection, and pulmonary hypertension. The analysis herein evaluated the safety and efficacy of the thrombopoietin receptor agonist romiplostim in splenectomized and nonsplenectomized adults with primary immune thrombocytopenia. Data were pooled across 13 completed clinical studies in adults with immune thrombocytopenia from 2002-2014. Adverse event rates were adjusted for time of exposure. Results were considered different when 95% confidence intervals were non-overlapping. Safety was analyzed for 1111 patients (395 splenectomized; 716 nonsplenectomized) who received romiplostim or control (placebo or standard of care). At baseline, splenectomized patients had a longer median duration of immune thrombocytopenia and a lower median platelet count, as well as a higher proportion with >3 prior immune thrombocytopenia treatments versus nonsplenectomized patients. In each treatment group, splenectomized patients used rescue medications more often than nonsplenectomized patients. Platelet response rates (≥50×109/L) for romiplostim were 82% (310/376) for splenectomized and 91% (592/648) for nonsplenectomized patients (P<0.001 by Cochran-Mantel-Haenszel test). Platelet responses were stable over time in both subgroups. Exposure-adjusted adverse event rates were higher for control versus romiplostim for both splenectomized (1857 versus 1226 per 100 patient-years) and nonsplenectomized patients (1052 versus 852 per 100 patient-years). In conclusion, responses to romiplostim were seen in both splenectomized and nonsplenectomized patients, and romiplostim was not associated with an increase in the risk of adverse events in splenectomized patients. clinical-trials.gov I

Virtual learning spaces provide the opportunity to create authentic, immersive and high-fidelity experiences for learners; often enhanced with new technology to increase the interaction and perception with the learning space. Instead of creating mock-ups in classrooms, educators are able to recreate a controlled replica of the real world, i.e. scenarios and situations can be created that are difficult or impossible to achieve otherwise. However, an unrestricted and unsupervised exploration imposes challenges to monitor the learner, offer supportive guidance and provide formative feedback. Preliminary studies demonstrated that different approaches are able to engage the learner, create an intrinsic motivation and therefore provide curiosity to drive the self-paced learning; yet the use-case-based exploration is not transferred to a framework including a comprehensive tool for education. In this chapter, we demonstrate the prototype of the nDiVE framework, which combines authentic education, gamification, emerging technology and design principles used in the game industry to create an engaging learning space for students and workers.

OBJECTIVES: The aim of this research is to assess causes and circumstances of deaths in extremely low gestational age neonates (ELGANs) born in Switzerland over a 3-year period. DESIGN: Population-based, retrospective cohort study. SETTING: All nine level III perinatal centres (neonatal intensive care units (NICUs) and affiliated obstetrical services) in Switzerland. PATIENTS: ELGANs with a gestational age (GA) <28 weeks who died between 1 July 2012 and 30 June 2015. RESULTS: A total of 594 deaths were recorded with 280 (47%) stillbirths and 314 (53%) deaths after live birth. Of the latter, 185 (59%) occurred in the delivery room and 129 (41%) following admission to an NICU. Most liveborn infants dying in the delivery room had a GA ≤24 weeks and died following primary non-intervention. In contrast, NICU deaths occurred following unrestricted life support regardless of GA. End-of-life decision-making and redirection of care were based on medical futility and anticipated poor quality of life in 69% and 28% of patients, respectively. Most infants were extubated before death (87%). CONCLUSIONS: In Switzerland, most deaths among infants born at less than 24 weeks of gestation occurred in the delivery room. In contrast, most deaths of ELGANs with a GA ≥24 weeks were observed following unrestricted provisional intensive care, end-of-life decision-making and redirection of care in the NICU regardless of the degree of immaturity.

Summary: Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.Copyright © 2014 John Wiley & Sons Ltd.

Anaplastic lymphoma kinase (ALK)-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, occur. Crizotinib inhibits ALK in vitro and in vivo and was administered as monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy. The overall response rate was 10 of 11 (90.9%; 95% confidence interval [CI] = 58.7% to 99.8%). Disease status at the latest follow-up is as follows: four patients are in complete response (CR) (months >21, >30, >35, >40) under continuous crizotinib administration; 4 patients had progression of disease (months 1, 2, 2, 2); 1 patient obtained CR on crizotinib, received an allogeneic bone marrow transplant, and is in CR; 2 patients (treated before and/or after allogeneic bone marrow transplant) obtained and are still in CR but they have stopped crizotinib. Overall and progression-free survival rates at 2 years are 72.7% (95% CI = 39.1% to 94.0%) and 63.7% (95% CI = 30.8% to 89.1%), respectively. ALK mutations conferring resistance to crizotinib in vitro could be identified in relapsed patients. Crizotinib exerted a potent antitumor activity with durable responses in advanced, heavily pretreated ALK+ lymphoma patients, with a benign safety profile.

A method for locating phase to ground faults in DC distribution systems. The method includes utilizing wavelet analysis using Multi-Resolution Analysis (MRA) as a signal processing tool for recognition of characteristic features in the voltage signal. The voltage signal contains characteristic information in the high frequency range above the switching frequencies of the PE converters which allows for localization of the fault.

A method for locating phase to ground faults in DC distribution systems. The method includes utilizing wavelet analysis using Multi-Resolution Analysis (MRA) as a signal processing tool for recognition of characteristic features in the voltage signal. The voltage signal contains characteristic information in the high frequency range above the switching frequencies of the PE converters which allows for localization of the fault.

Electrodynamics Associates (EA) is developing a MW-class high-speed generator and requires testing of the corresponding excitation controller at Florida State University's (FSU) Center for Advanced Power Systems (CAPS) in a controller hardware-in-the-loop (CHIL) environment. The goal of these tests is to verify the functionality of the generator excitation controller prior to a full scale power hardware-in- the-loop (PHIL) test of the entire generator. Such tests will become feasible at FSU-CAPS in spring of 2010 as the center is currently procuring a gear system that will extend the shaft speed range of the existing 5 MW PHIL facility for rotating machinery from 450 rpm up to 24,000 rpm. This paper focuses on the CHIL testing of the primary excitation system controller, in which the secondary excitation power supply, the main generator, the prime mover, and the load were simulated on a real time computer simulator and interfaced to the controller. Simulating the high-speed generator in real-time is especially challenging since non real-time simulation models of such rotating machines typically contain relatively small time constants which pose challenges to real-time simulation algorithms. The paper discusses approaches to overcome these challenges. In addition, the plans and considerations for PHIL testing of the generator are addressed. This setup will enable, for the first time in a laboratory setup, PHIL testing of a MW scale high-speed generator with a realistic representation of its surrounding dynamic environment.

BACKGROUND: Because ethical decision making in the care of extremely preterm infants varies widely across Europe, the Swiss Society of Neonatology decided to publish its own guidelines on the care of infants born at the limit of viability in 2002. OBJECTIVE: To examine the potential impact of the guidelines on survival rates, short-term complication rates and centre-to-centre outcome differences of extremely preterm infants (22-25 completed weeks). DESIGN: Population-based, retrospective cohort study. SETTING: All nine level III neonatal intensive care units (NICU) and affiliated paediatric hospitals in Switzerland. PATIENTS: 516 extremely preterm infants born alive between 1 January 2000 and 31 December 2004. MAIN OUTCOME MEASURES: Delivery room and NICU mortality rates, survival to hospital discharge and incidence of short-term complications in survivors were assessed. To study the impact of the guidelines, two cohorts from two different time periods were compared (years 2000/2001, n = 220; years 2003/2004, n = 204) whereas patients born in the year of the publication (2002, n = 92) were excluded. For centre-to-centre comparisons, the entire population (n = 516) was analysed. RESULTS: There was a significant increase in survival rates of extremely preterm infants from 31% to 40% (RR 1.24, 95% CI 1.02, 1.50) after the publication of the Swiss guidelines. This improvement was largely explained by significantly improved survival from 42% to 60% (p = 0.01) among infants born at 25 completed weeks because of decreased NICU mortality. Improved survival was not associated with statistically significant changes in the incidence of short-term complications. Despite national guidelines, considerable centre-to-centre outcome differences have persisted. CONCLUSIONS: The publication of the Swiss guidelines was followed by significantly improved survival of extremely preterm infants but had no impact on centre-to-centre differences.

Einleitung: Eine Strategie zur Veringerung von pemanenten Paresen des N. laryngeus recurrens (RLNP) in der Schildrüsenchirurgie ist die obligate Nervenpräparation. Der Effekt des intraoperativen Neuromonitorings (IONM) des N. laryngeus reccurrens (RLN) ist noch immer unklar.Methoden: Es wurden 913 Patienten mit Hemithyroidectomie oder totaler Thyroidektomie mit 1602 gefährdeten Nerven (NAR) mittels Laryngoskopie und Videostroboskopie prea- und postoperativ prospektiv untersucht. In jedem Fall wurde eine langstreckige Präparation des RLN vorgenommen. Dabei wurde kein IONM eingesetzt. Benigne (BT) (1014 NAR) und maligne Schilddrüsenerkrankungen (MT) (578 NAR) wurden getrennt analysiert. Eine RLNP wurde nicht vor 2 Jahren ihres Bestehens als permanent bezeichnet.Ergebnisse: Es wurden 2,6% und 4,5% temporäre RLNPs je Nerv in der BT bzw. MT Gruppe identifiziert, und nur 0,3% und 0,9% an permanenten RLNPs in den jeweiligen Gruppen.Schlussfolgerungen: In den meisten Studien mit Nervenpräparation war die Rate an RLNPs (temporär und permanent) niedriger als in solchen ohne Durchführung einer Nervenpräparation. Hingegen zeigten Studien mit IONM keine Verbesserung der Rate. Eine obligate Nervenpräparation verringert also die Anzahl permanenter RLNP wirksam. Neben der indirekten Laryngoskopie sollte bei allen Patienten mit nicht eindeutig normaler beidseitiger Larynxfunktion und Stimmqualität unbedingt eine Videostroboskopie durchgeführt werden, um Fehldiagnosen zu vermeiden.

Einleitung: Eine Strategie zur Veringerung von pemanenten Paresen des N. laryngeus recurrens (RLNP) in der Schildrüsenchirurgie ist die obligate Nervenpräparation. Der Effekt des intraoperativen Neuromonitorings (IONM) des N. laryngeus reccurrens (RLN) ist noch immer unklar.Methoden: Es wurden 913 Patienten mit Hemithyroidectomie oder totaler Thyroidektomie mit 1602 gefährdeten Nerven (NAR) mittels Laryngoskopie und Videostroboskopie prea- und postoperativ prospektiv untersucht. In jedem Fall wurde eine langstreckige Präparation des RLN vorgenommen. Dabei wurde kein IONM eingesetzt. Benigne (BT) (1014 NAR) und maligne Schilddrüsenerkrankungen (MT) (578 NAR) wurden getrennt analysiert. Eine RLNP wurde nicht vor 2 Jahren ihres Bestehens als permanent bezeichnet.Ergebnisse: Es wurden 2,6% und 4,5% temporäre RLNPs je Nerv in der BT bzw. MT Gruppe identifiziert, und nur 0,3% und 0,9% an permanenten RLNPs in den jeweiligen Gruppen.Schlussfolgerungen: In den meisten Studien mit Nervenpräparation war die Rate an RLNPs (temporär und permanent) niedriger als in solchen ohne Durchführung einer Nervenpräparation. Hingegen zeigten Studien mit IONM keine Verbesserung der Rate. Eine obligate Nervenpräparation verringert also die Anzahl permanenter RLNP wirksam. Neben der indirekten Laryngoskopie sollte bei allen Patienten mit nicht eindeutig normaler beidseitiger Larynxfunktion und Stimmqualität unbedingt eine Videostroboskopie durchgeführt werden, um Fehldiagnosen zu vermeiden.