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

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

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

Understanding differences between summer vs. school obesogenic behaviors of children: the structured days hypothesis

Abstract Background Although the scientific community has acknowledged modest improvements can be made to weight status and obesogenic behaviors (i.e., physical activity, sedentary/screen time, diet, and sleep) during the school year, studies suggests improvements are erased as elementary-age children are released to summer vacation. Emerging evidence shows children return to school after summer vacation displaying accelerated weight gain compared to the weight gained occurring during the school year. Understanding how summer days differ from when children are in school is, therefore, essential. Discussion There is limited evidence on the etiology of accelerated weight gain during summer, with few studies comparing obesogenic behaviors on the same children during school and summer. For many children, summer days may be analogous to weekend days throughout the school year. Weekend days are often limited in consistent and formal structure, and thus differ from school days where segmented, pre-planned, restrictive, and compulsory components exist that shape obesogenic behaviors. The authors hypothesize that obesogenic behaviors are beneficially regulated when children are exposed to a structured day (i.e., school weekday) compared to what commonly occurs during summer. This is referred to as the ‘Structured Days Hypothesis’ (SDH). To illustrate how the SDH operates, this study examines empirical data that compares weekend day (less-structured) versus weekday (structured) obesogenic behaviors in U.S. elementary school-aged children. From 190 studies, 155 (~80%) demonstrate elementary-aged children’s obesogenic behaviors are more unfavorable during weekend days compared to weekdays. Conclusion In light of the SDH, consistent evidence demonstrates the structured environment of weekdays may help to protect children by regulating obesogenic behaviors, most likely through compulsory physical activity opportunities, restricting caloric intake, reducing screen time occasions, and regulating sleep schedules. Summer is emerging as the critical period where childhood obesity prevention efforts need to be focused. The SDH can help researchers understand the drivers of obesogenic behaviors during summer and lead to innovative intervention development