Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Effects of pentoxifylline on exercising skeletal muscle vascular control in rats with chronic heart failure

Master of ScienceDepartment of KinesiologyTimothy I. MuschBoth cardiac and peripheral vasculature dysfunction likely contribute, in part, to elevations in TNF-[alpha] and exercise intolerance in chronic heart failure (CHF). The pharmaceutical TNF-[alpha] synthesis suppressor pentoxifylline (PTX) reduces plasma [TNF-[alpha]] and improves left ventricular (LV) function in CHF rats, but the effects of PTX on skeletal muscle blood flow (BF) and vascular conductance (VC) during exercise are unknown. We tested the hypothesis that PTX would elevate skeletal muscle BF and VC at rest and during submaximal treadmill exercise in CHF rats (coronary artery ligation). CHF rats received i.p. injections of 30 mg·kg[superscript]-[superscript]1·day[superscript]-[superscript]1 of PTX (CHF+PTX, n=13) or saline (CHF, n=8) for 21 days. Mean arterial pressure (MAP) and BF (radiolabeled microsphere infusions) were measured at rest and during treadmill exercise (20 m/min, 5% grade). Myocardial infarct (MI) size was not different between groups (CHF: 37±4, CHF+PTX: 37±3% of LV wall; p>0.05). Resting and exercising MAP was greater in CHF+PTX compared to CHF (p0.05). However, during exercise PTX increased total hindlimb BF (CHF: 83±9, CHF+PTX: 114±8 ml·min[superscript]-[superscript]1·100g[superscript]-[superscript]1, p<0.05) and VC (CHF: 0.75±0.08, CHF+PTX: 0.88±0.06 ml·min[superscript]-[superscript]1·100g[superscript]-[superscript]1·mmHg[superscript]-[superscript]1, p<0.05). Furthermore, exercising BF was increased in 21, and VC in 11, of the 28 individual hindlimb muscles or muscle parts with no apparent fiber-type specificity. Thus, PTX administration augments skeletal muscle BF and VC during locomotory exercise in CHF rats, which carries important therapeutic implications for CHF patients

Level of perception of nurses regarding family-witnessed resuscitation

The researchers used the descriptive research design where the respondents were nurses employed at De La Salle University Medical Center. The study used convenience or accidental sampling and a modified-adapted questionnaire from Koberich and colleagues (2010) as research instrument. Data was analysed using percentage, frequency distribution, and chi-square test. Most of the respondents were female and were aged 21-30 years old, have 0-5 years of clinical experience and majority were assigned at the emergency department. The level of perception of nurses regarding family-witnessed resuscitation was positive. There were no significant differences in the level of perception of nurses regarding family-witnessed resuscitation in terms of age, gender, years of clinical experience and area of assignment

Co-designing and piloting an Integrated Digital Literacy and Language Toolkit for vulnerable migrant students in higher education

This paper presents the process of co-design, co-production, piloting, evaluation and revision of an Integrated Digital Literacy and Language Toolkit for Vulnerable Migrant Students (VMs) in Higher Education (HE). The language element focuses on academic language skills of reading, writing, listening and speaking required for efective involvement in both the host society and HE learning; the acquisition and improvement of digital literacy skills enable VMs to successfully participate in, and contribute to, university and societal collaboration, creativity and content curation. The Toolkit resulted from the co -operation and collaboration of fve EU universities and was based on the ASSURE instructional design model. The Toolkit ofers a selfaccess, self- paced, non-linear, fully online set of ten stand-alone units which ofer a range of materials and activities to develop those skills pertinent to VM academic language and digital literacy needs. Evaluation by a group of VMs resident in EU countries highlight the positive impact of the Toolkit and validates the instrument as ft for purpose. Noteworthy aspects include its usefulness in supporting student autonomy, improving digital capabilities and academic language mastery,a positive experience of a fexible learning experience along with access to open resources of international scope and dissemination under the Creative Commons licence.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer NatureEAC/A05/2017: ERASMUS+ KA2KA203 Strategic Partnerships for higher education2.917 JCR (2020) Q2, 85/265 Education & Educational Research1.055 SJR (2021) Q1, 181/1381 EducationNo data IDR 2020UE

The conservation status of the world’s reptiles

Effective and targeted conservation action requires detailed information about species, their distribution, systematics and ecology as well as the distribution of threat processes which affect them. Knowledge of reptilian diversity remains surprisingly disparate, and innovative means of gaining rapid insight into the status of reptiles are needed in order to highlight urgent conservation cases and inform environmental policy with appropriate biodiversity information in a timely manner. We present the first ever global analysis of extinction risk in reptiles, based on a random representative sample of 1500 species (16% of all currently known species). To our knowledge, our results provide the first analysis of the global conservation status and distribution patterns of reptiles and the threats affecting them, highlighting conservation priorities and knowledge gaps which need to be addressed urgently to ensure the continued survival of the world’s reptiles. Nearly one in five reptilian species are threatened with extinction, with another one in five species classed as Data Deficient. The proportion of threatened reptile species is highest in freshwater environments, tropical regions and on oceanic islands, while data deficiency was highest in tropical areas, such as Central Africa and Southeast Asia, and among fossorial reptiles. Our results emphasise the need for research attention to be focussed on tropical areas which are experiencing the most dramatic rates of habitat loss, on fossorial reptiles for which there is a chronic lack of data, and on certain taxa such as snakes for which extinction risk may currently be underestimated due to lack of population information. Conservation actions specifically need to mitigate the effects of human-induced habitat loss and harvesting, which are the predominant threats to reptiles