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

Inequalities in Access to Educational Opportunities: An Investigation of the PISA 2009 Dataset using a Multilevel-IRT Framework

A fundamental goal in education is to provide access to quality education and educational opportunities for every student. Classroom processes, teaching, and students’ learning experiences are at the heart of quality education and, as such, must be the key focus in investigating the issues of equity in access to education (O’Sullivan, 2006; Peske & Haycock, 2006; Raudenbush & Sadoff, 2008). In light of India’s performance in PISA 2009, this dissertation study investigates the larger issues of access to high quality teaching practices, and other valuable school resources to get a better picture of India’s poor performance. To this end, publicly available large-scale datasets such as the Programme of International Student Achievement (PISA; by OECD), and the Teaching and Learning International Survey (TALIS; by OECD) enable us to look beyond student’s achievement scores or a country’s ranking by providing us with a plethora of information on students, teachers, and schools. Moreover, even though PISA assessments are low stakes tests, they often drive high stakes education policy decisions in multiple countries.In this dissertation study, I make use of the PISA student and school questionnaires for India along with state-of the art multilevel IRT models implemented using MCMC. I describe and illustrate a methodology to examine students’ exposure to key instructional practices based on students’ responses to PISA survey items, and then use this measure as an outcome variable in a three-level IRT model to investigate differences in the amounts of exposure to key practices within schools and between schools. Measurement invariance was established across the rural and urban regions of Himachal Pradesh (HP) and Tamil Nadu (TN) before comparing the construct of interest across various sub-groups. This set of analyses indicates that the items in the student questionnaires capture the construct of interest, and are not an artifact of underlying translation errors, or cultural differences in the examinees understanding of these items. A multilevel IRT approach, such as the one employed in this dissertation allows us to tease apart the variation in the extent to which students experience particular instructional practices into their within-school and between-school components. The analysis strategies developed in connection with my dissertation will hopefully be valuable to other researchers interested in investigating questions concerning inequality in the distribution of key instructional practices.Lastly, in chapter 6, I depict the use of this approach to identify schools, whose students on an average, experience relatively high or low exposure to the instructional practices of interest. Futhermore, a key finding of this set of analyses indicated that the that a majority of the public or government-run schools were concentrated in the lowest end of the socio-economic scale; private schools were found to be more spread out, but still in low socio-economic areas

Pediatric sciatic neuropathies due to unusual vascular causes

Four cases of pediatric sciatic neuropathies due to unusual vascular mechanisms are reported. Pediatric sciatic neuropathies were seen after umbilical artery catheterization, embolization of arteriovenous malformation, meningococcemia, and hypereosinophilic vasculitis. Electrophysiologic studies demonstrated abnormalities in motor studies of peroneal and tibial nerves. Sensory studies demonstrated abnormalities of sural and superficial peroneal nerves. Results of needle electromyography were abnormal in sciatic-innervated muscles. Prognosis was variable and depended on the severity of the initial nerve injury

Investigating the relationship between participation in the building infrastructure leading to diversity (BUILD) initiative and intent to pursue a science career: A cross-sectional analysis.

This paper presents an analysis of survey data to examine the association between supervised structured mentoring and students intent to pursue a career in science. Data were collected from students in the 10 Building Infrastructure Leading to Diversity (BUILD) research training programs, developed through grants from the National Institutes of Health. Propensity score matching and multinomial logistic regression demonstrated that exposure to BUILD programs-meaning participation in undergraduate research, receipt of mentoring from a primary mentor, and/or participation as a funded scholar and/or associate of each BUILD sites training program-was associated with increased intent to pursue a science career. These findings have implications for STEM program evaluation and practice in higher education

The effect of losigamone (AO-33) on electrical activity and excitatory amino acid release in mouse cortical slices

1. Losigamone is a novel anticonvulsant the mechanism of action of which is not known. This study investigated the effect of losigamone on spontaneous, NMDA- and AMPA-induced depolarizations in the cortical wedge preparation of the DBA/2 mouse (which are susceptible to sound-induced seizures) and on endogenous amino acid release from BALB/c mouse cortical slices. 2. Cortical wedges exhibit spontaneous depolarizations in magnesium-free medium and losigamone was effective in significantly reducing these spontaneous depolarizations at concentrations of 100 μM and above. 3. NMDA-induced depolarizations were significantly reduced by losigamone at concentrations of 25 μM and above. Losigamone had no effect on AMPA-induced depolarizations. 4. Veratridine (20 μM) and potassium (60 mM) were used to stimulate the release of amino acids from mouse cortex. Veratridine-stimulated release of glutamate was significantly reduced by losigamone at concentrations of 100 μM and above, while potassium-stimulated release was significantly reduced by losigamone at 200 μM. 5. NMDA antagonism and inhibition of excitatory amino acid release may contribute to the anticonvulsant effect of losigamone

Leprosy-associated chronic wound management using biomaterials

Background: Deformities and neuropathic chronic ulcers are the common features associated with leprosy-cured individuals that impact their quality of life and impair rehabilitation efforts. The challenging aspects for treatment of chronic wounds are the factors that inhibit healing. We reasoned that limited success of various therapeutic interventions could be due to the fact that leprosy-cured individual's physiology gets acclimatized to having a chronic wound that any therapeutic intervention is counterbalanced to maintain status quo at the wound site. Therefore, an alternative strategy would be to use biomaterials that gradually alter the wound site allowing the individual's physiology to participate in the healing process. Aims: Developing the human amnion (Amn)-derived biomaterial scaffolds and evaluating its use to heal chronic wounds in leprosy-cured but deformed persons (LCDPs). Materials and Methods: Using an enzymatic protocol, we have developed a rapid method to generate biomaterial scaffolds from discarded human Amn. A clinical trial on 26 LCDPs was performed with the biomaterial, and its wound-healing potential was then compared with LCDPs undergoing standard treatment procedure. Results: Biomaterial-based treatment of chronic wounds on LCDP displayed a higher efficiency in healing when compared to standard treatment. Conclusions: This study exemplifies that biomaterial-based treatment of leprosy-wounds offers an excellent affordable alternative for wound management. This study underlines the importance of involving both local wound environment and systemic effects for healing. In addition, we highlight wound healing as a necessity for successful rehabilitation and reintegration of leprosy-cured person into the society